Tridoshas viz Vata, Pitta, and Kapha are responsible for health and disease depending on their normalcy and disequilibrium state. Improper usage of foods and drinks along with abnormal activities manifests diseases of respective Doshik predominance. Sira (vein) is the synonym of Srotas, keeping this in mind, Vatavaha Sira is correlated with Vatavaha Srotas, Pittavaha Sira with Pittavaha Srotas, Kaphavaha Sira with Kaphavaha Srotas, and Sarvavaha Sira with Sarvavaha Srotas. The purpose of detail understanding of Doshavaha Srotas is essential to understand the role of Doshas in the manifestation of diseases. One can easily predict by observing the color changes in particular area to be able to predict the predominance of Doshas in that area. Manifestation of a disease occurs in the body as a result of the defective Srotas favoring the Dosha–Dushya conglomeration. Hence, any defect in the Srotas must be corrected quickly for the restoration of normal health. Present article emphasis on the proper understanding of Doshavaha Srotas in a systematic manner to understand its root, causative factors, signs and symptoms, and diseases produced due to their vitiation.
Kapha; nanatmaja vikara; pitta; Sarvavaha Srotas; sira; vata
Urinary incontinence (UI) is a disease affecting quality of life of 200 million patients worldwide. It is characterized by involuntary loss of urine. The factors involved are cystitis, detrusor hyperreflexia, spinal injury, benign prostatic hyperplasia, etc. The surge in the number of reviews on this subject indicates the amount of research devoted to this field. The prevalence is increasing at an alarming rate but unfortunately, only a few medications are currently available for this condition. There are peripheral as well as central targets including cholinergic, vanilloid, prostaglandin, kinin, calcium channel, cannabinoid, serotonin, and GABA-receptors, which act by different mechanisms to treat different types of incontinence. Drugs acting on the central nervous system (CNS) increase urinary bladder capacity, volume, or pressure threshold for micturition reflex activation while peripherally acting drugs decrease the amplitude of micturition contraction and residual volume. Anticholinergic drugs specifically M3 receptor antagonists are the first choice but have frequent side effects such as dry mouth, CNS disturbances, etc. Therefore, there is a need to understand the biochemical pathways that control urinary dysfunction to determine the potential to which they can be exploited in the treatment of this condition. This article reviews the central and peripheral molecular targets and the potential therapeutic approaches to the treatment of UI.
Detrusor muscle; incontinence; molecular targets; overactive bladder
The vast majority of patients with multiple sclerosis (MS) develop bladder control problems including urgency to urinate, urinary incontinence, frequency of urination, and retention of urine. Over 60% of MS patients show detrusor-sphincter dyssynergia, an abnormality characterized by obstruction of urinary outflow as a result of discoordinated contraction of the urethral sphincter muscle and the bladder detrusor muscle. In the current study we examined bladder function in female SWXJ mice with different defined levels of neurological impairment following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of central nervous system inflammation widely used in MS research. We found that EAE mice develop profound bladder dysfunction characterized by significantly increased micturition frequencies and significantly decreased urine output per micturition. Moreover, we found that the severity of bladder abnormalities in EAE mice was directly related to the severity of clinical EAE and neurologic disability. Our study is the first to show and characterize micturition abnormalities in EAE mice thereby providing a most useful model system for understanding and treating neurogenic bladder.
EAE/MS; autoimmune; micturition; neurogenic bladder
The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain and spinal cord that coordinates the activity of the bladder and urethral outlet. Experimental studies in animals indicate that urine storage is modulated by reflex mechanisms in the spinal cord, whereas voiding is mediated by a spinobulbospinal pathway passing through a coordination centre in the rostral brain stem. Many of the neural circuits controlling micturition exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. This study summarizes the anatomy and physiology of the spinal and supraspinal micturition switching circuitry and describes a computer model of these circuits that mimics the switching functions of the bladder and urethra at the onset of micturition.
brain stem; spinal cord; switching circuit
This study represents the first paper of the effects of growth regulators on the physiochemical and phytochemical properties of the wax apple fruit, a widely cultivated fruit tree in southeast Asia. Net photosynthesis, sucrose phosphate synthase (SPS) activity, peel color, fruit firmness, juice content, pH value, total soluble solids (TSSs), and the sugar acid ratio were all significantly increased in growth regulators (PGRs) treated fruits. The application of gibberellin (GA3), naphthalene acetic acid (NAA), and 2,4-dichlorophenoxy acetic acid (2,4-D) significantly reduced titratable acidity and increased total sugar and carbohydrate content compared to the control. The 50 mg/L GA3, 10 mg/L NAA, and 5 mg/L 2,4-D treatments produced the greatest increases in phenol and flavonoid content; vitamin C content was also higher for these treatments. PGR treatment significantly affected chlorophyll, anthocyanin, and carotene content and produced higher phenylalanine ammonia lyase (PAL) and antioxidant activity levels. There was a positive correlation between peel color and TSS and antioxidant activity and both phenol and flavonoid content and PAL activity and anthocyanin formation. A taste panel assessment was also performed, and the highest scores were given to fruits that had been treated with GA3 or auxin. The study showed that application of 50 mg/L GA3, 10 mg/L NAA, and 5 mg/L 2,4-D once a week from bud development to fruit maturation increased the physiochemical and phytochemical properties of wax apple fruits.
Total renal ammonia production and ammonia precursor utilization were evaluated in patients under normal acid-base balance and in patients with 24-h NH4Cl acidosis by measuring (a) ammonia excreted with urine and that added to renal venous blood, and (b) amino acid exchange across the kidney. In 24-h acidosis not only urinary ammonia excretion is increased, but also total ammonia production is augmented (P less than 0.005) in comparison with controls. By evaluating the individual role of acid-base parameters, urine pH and urine flow in influencing renal ammonia production, it was shown that the degree of acidosis and urine flow are likely major factors stimulating ammoniagenesis. Both urine pH and urine flow are determinant in the preferential shift of ammonia into urine. In 1-d acidosis, renal extraction of glutamine was not increased and the total ammonia produced/glutamine N extracted ratio was higher than in controls (P less than 0.005) and was inversely correlated with the log of arterial bicarbonate concentration (P less than 0.001). In the same condition, renal glycine and ornithine uptake took place; the more severe the acidosis, the greater was the renal extraction of these amino acids (P less than 0.001). These data indicate that at the early stages of metabolic acidosis, in spite of a brisk increase in ammonia production, the mechanisms responsible for the increased glutamine use, which are operative in chronic acidosis, are not activated and other ammonia precursors, besides glutamine, are probably used for ammonia production.
Measurements of urinary flow rate were performed in 16 patients with established prostatitis before and after a course of antimicrobial therapy. Before treatment the maximum flow rates were poor with abnormal flow curves and significant improvement in voiding characteristics were observed with treatment (P less than 0.01). A preliminary electrophysiological (EMG) study of sphincter activity suggested that the obstruction to the flow of urine was at least in part due to failure of the external sphincter to relax during micturition. Although the total number of cases in this series was small the study showed that prostatitis was associated with a disorder of micturition which correlated with the other clinical features of the disease and could be objectively evaluated. Eradication of infection restored normal conditions in the lower urinary tract.
Pituitary adenylate cyclase activating polypeptide (PACAP) and receptors are expressed in micturition pathways. Studies demonstrated roles for PACAP in detrusor smooth muscle contraction, facilitating ATP release from urothelium and PACAP antagonism reduced cyclophosphamide-induced bladder hyperreflexia.
Materials and Methods
PACAP contributions to micturition and somatic sensation were studied in PACAP knockout (PACAP−/−), littermate heterozygote (PACAP+/−) and wildtype (WT) mice using conscious cystometry with continuous intravesical saline or acetic acid (AA; 0.5%) instillation, urination patterns, somatic sensitivity testing of hindpaw and pelvic region with calibrated von Frey filaments and morphological assessments of urinary bladder.
PACAP−/− mice exhibit increased bladder mass with fewer but larger urine spots. In PACAP−/− mice, the lamina propria and detrusor smooth muscle are significantly thicker whereas the urothelium is unchanged. PACAP−/− mice exhibit increased bladder capacity, void volume (VV) and longer intercontraction interval (ICI) with significantly increased detrusor contraction duration and large residual volume. WT mice respond to AA (0.5%) with a reduction in VV and a decreased ICI whereas PACAP+/− and PACAP−/− mice do not respond. PACAP−/− mice are less responsive to somatic stimulation. PACAP+/− also exhibit bladder dysfunction and somatic and visceral sensory abnormalities but to a lesser degree.
PACAP gene disruption contributes to changes in bladder morphology, bladder function and somatic and visceral hypoalgesia.
cystometry; pelvic sensitivity; hindpaw sensitivity; nociceptive reflexes
Trospium chloride is a quaternary ammonium compound, which is a competitive antagonist at muscarinic cholinergic receptors. Preclinical studies using porcine and human detrusor muscle strips demonstrated that trospium chloride was many-fold more potent than oxybutynin and tolterodine in inhibiting contractile responses to carbachol and electrical stimulation. The drug is poorly bioavailable orally (< 10%) and food reduces absorption by 70%– 80%. It is predominantly eliminated renally as unchanged compound. Trospium chloride, dosed 20 mg twice daily, is significantly superior to placebo in improving cystometric parameters, reducing urinary frequency, reducing incontinence episodes, and increasing urine volume per micturition. In active-controlled trials, trospium chloride was at least equivalent to immediate-release formulations of oxybutynin and tolterodine in efficacy and tolerability. The most problematic adverse effects of trospium chloride are the anticholinergic effects of dry mouth and constipation. Comparative efficacy/tolerability data with long-acting formulations of oxybutynin and tolterodine as well as other anticholinergics such as solifenacin and darifenacin are not available. On the basis of available data, trospium chloride does not appear to be a substantial advance upon existing anticholinergics in the management of urge urinary incontinence.
urge incontinence; trospium; anticholinergic; overactive bladder
The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs.
Micturition; Urinary bladder; Nerve growth factor; Urethra sphincter; Neurogenic detrusor overactivity; Detrusor-sphincter-dyssynergia; Afferent nerves; Synaptic remodeling; Neuropeptides; Urothelium
To investigate the effect of sensory neuron-specific receptors (SNSRs) activation on the micturition reflex in rats.
MATERIALS AND METHODS
Continuous cystometrograms (CMG, 0.04ml/min) were performed in female Sprague-Dawley rats under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8–22 (BAM8-22), was administered intravenously or intrathecally in normal rats or rats pretreated with capsaicin 4 days before the experiments. Micturition parameters were recorded and compared before and after drug administration.
Intravenous administration of BAM8-22 (3 to 100 μg/kg) significantly increased intercontraction intervals in dose dependent fashion, but did not affect residual urine or baseline pressure at any doses tested. Intrathecal administration of BAM8-22 (0.01 to 0.3 μg) also increased intercontraction intervals in dose dependent fashion, but did not affect residual urine or baseline pressure at any doses tested. These inhibitory effects of intravenous (30 μg/kg) or intrathecal (0.3 μg) administration of BAM8-22 were still observed after capsaicin pretreatment.
These results indicate that in urethane-anesthetized rats activation of SNSRs can inhibit the micturition reflex via the pathways independent of capsaicin sensitive C-fibers. Thus SNSRs could be a potential target for the treatment of bladder dysfunction such as overactive bladder.
bladder; sensory-neuron-specific receptors; capsaicin; spinal cord; rats
OBJECTIVES—To examine the frequency and
pathophysiology of micturitional disturbance in patients with
METHODS—Micturitional symptoms were noted
and neurological examinations made repeatedly during admission to
hospital of patients with clinical and neurophysiologically definite
Guillain-Barré syndrome. Urodynamic studies consisted of
uroflowmetry, measurement of residual urine, urethral pressure
profilometry, medium fill water cystometry, and external sphincter EMG.
RESULTS—Seven of 28 (25%) patients with
Guillain-Barré syndrome showed micturitional disturbance. The
symptoms included voiding difficulty in six, urinary retention in
three, nocturnal urinary frequency in three, and urge incontinence in
two. These micturitional symptoms appeared after weakness occurred, and
improved gradually along with the neurological signs. All three
patients who showed retention became able to urinate. Urodynamic
studies were made on four symptomatic patients two of whom underwent
repeated study. Disturbed bladder sensation was noted in one patient,
bladder areflexia in one, and absence of the bulbocavernosus reflex in
one. Cystometry showed decreased bladder volume in two and bladder
overactivity in two, one of whom had urge urinary incontinence and the
other urinary retention.
CONCLUSIONS—A quarter of the patients with
Guillain-Barré syndrome tend to have micturitional disturbance. The
patients studied had evacuation and storage disorders, as well as
bladder areflexia and disturbed bladder sensation indicative of
peripheral types of parasympathetic and somatic nerve dysfunction.
Decreased bladder volume with bladder overactivity but no evidence of
CNS involvement was also found, evidence that bladder overactivity also
occurs in peripheral nerve lesions with probable pelvic nerve irritation.
Ayurveda symbolises holistic approach towards treating diseases and better prevention than cure as its one of the main motto.1 In present paper, etiological based survey of 30 patients was carried out to assess dietary and habitual lifestyles of people suffering from hypertension, for this a detailed proforma based on classical etiological factors related to hypertension was used. After the detailed assessment it was found that, more percentage of etiological factors of Raktavaha Srotas (micro channels for the transportation of blood) (78.46%), Rasavaha Srotas (micro channels for the transport of chyme) (53.33%) were found influenced than that ofManovaha Srotas (micro channels for the conveyance of psyche) (27.67%)) and Medovaha Srotas (micro channels transporting of fats) (37.76%). Hence, it can be concluded that avoidance of these etiologies (Nidanaparivarjana) is a first step in the direction of control and management of hypertension.
In humans, the storage and voiding functions of the urinary bladder have a characteristic diurnal variation, with increased voiding during the day and urine storage during the night. However, in animal models, the daily functional differences in urodynamics have not been well-studied. The goal of this study was to identify key urodynamic parameters that vary between day and night. Rats were chronically instrumented with an intravesical catheter, and bladder pressure, voided volumes, and micturition frequency were measured by continuous filling cystometry during the light (inactive) or dark (active) phases of the circadian cycle. Cage activity was recorded by video during the experiment. We hypothesized that nocturnal rats entrained to a standard 12:12 light:dark cycle would show greater ambulatory activity and more frequent, smaller volume micturitions in the dark compared to the light. Rats studied during the light phase had a bladder capacity of 1.44±0.21 mL and voided every 8.2±1.2 min. Ambulatory activity was lower in the light phase, and rats slept during the recording period, awakening only to urinate. In contrast, rats studied during the dark were more active, had a lower bladder capacities (0.65±0.18 mL), and urinated more often (every 3.7±0.9 min). Average bladder pressures were not significantly different between the light and dark (13.40±2.49 and 12.19±2.85 mmHg, respectively). These results identify a day-night difference in bladder capacity and micturition frequency in chronically-instrumented nocturnal rodents that is phase-locked to the normal circadian locomotor activity rhythm of the animal. Furthermore, since it has generally been assumed that the daily hormonal regulation of renal function is a major driver of the circadian rhythm in urination, and few studies have addressed the involvement of the lower urinary tract, these results establish the bladder itself as a target for circadian regulation.
Coordination of the urinary bladder and the external urethral sphincter (EUS) is controlled by descending projections from the pons, and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents, traveling in the penile component of the somatic pudendal nerve, by electrical stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized male cats. Depending on the frequency of stimulation (range 1–40 Hz), activation of penile afferents either inhibited contractions of the bladder and promoted urine storage or activated the bladder and produced micturition. Stimulation of the DNP at 5–10 Hz inhibited distension evoked contractions and increased the maximum bladder capacity before incontinence. Conversely, stimulation at 33 and 40 Hz augmented distension evoked contractions. When the bladder was filled above a threshold volume (70% of the volume necessary for distension evoked contractions), stimulation at 20–40 Hz activated de novo the micturition reflex and elicited detrusor contractions that increased voiding efficiency compared to distension evoked voiding. Electrical stimulation of the DNP with a cuff electrode or percutaneous wire electrode produced similar results. The ability to evoke detrusor contractions by activation of the DNP was preserved following acute spinal transection. These results demonstrate a clear role of genital afferents in modulating the micturition reflex and suggest the DNP as a potential target for functional restoration of bladder control using electrical stimulation.
electrical stimulation; spinal cord injury; dorsal nerve of the penis; frequency-dependence
Xanthogranulomatous prostatitis is an unusual benign inflammatory process of prostate. Clinically it mimics prostatic carcinoma, requiring pathological examination for diagnosis.
A 60-year-old patient presented with 6 months history of increasing difficulty in micturition. On digital rectal examination prostate was hard and nodular and estimated weight was 50-gram. His serum prostate specific antigen (PSA) was 150 ng/ml. Clinically a locally advanced carcinoma of prostate was suspected. In view of severe obstructive urinary symptoms and significant post-micturition residual urine, transurethral resection of prostate was carried out. Histopathological examination of resected prostatic tissue revealed xanthogranulomatous prostatitis with no evidence of malignancy. Patient remains symptom free at 16 months follow-up and serum PSA has decreased to 6 ng/ml.
Xanthogranulomatous prostatitis is a benign inflammatory disorder of prostate that can clinically and even biochemically mimic prostatic carcinoma. A high degree of suspecion and close co-operation with pathologist is necessary for the diagnosis of xanthogranulomatous prostatitis.
The administration of vasodilating agents such as bradykinin and acetylcholine cause an increase in urinary sodium excretion. Yet the mechanisms involved in this natriuretic effect are not clear. Recent studies with another renal vasodilator, secretin have shown this drug also causes a profound increase in renal blood flow but without major changes in sodium excretion. To attempt to delineate the basis of this difference in sodium excretion with these drugs, the renal functional effects of secretin and bradykinin were compared at an equivalent vasodilating dose. Bradykinin increased renal blood flow from 222 to 342 ml/min, urine volume from 0.2 to 1.2 ml/min, and urine sodium excretion from 28 to 115 μeq/min. Urine osmolality fell from 1,230 to 401 mosmol/kg. Secretin caused a comparable increase in renal blood flow (216 to 325 ml/min) while changes in urine flow, sodium excretion, and urine osmolality were significantly less.
In further studies papillary plasma flow was estimated using the albumin accumulation technique. Control papillary plasma flow was 29 ml/min per 100 g. Bradykinin increased urinary sodium excretion 108 μeq/min and decreased urinary osmolality from 1,254 to 516 mosmol/kg in association with a rise in papillary plasma flow to 62 ml/min per 100 g. Urine sodium excretion, urinary osmolality, and urine flow rate, as well as papillary plasma flow rate (32 ml/min per 100 g) were unchanged from control when secretin was administered. Studies with acetylcholine were qualitatively similar to those of bradykinin. Renal blood flow increased from 150 to 248 ml/min, urinary sodium excretion increased from 20 to 243 μeq/min, urinary osmolality decreased from 1,237 to 411 mosmol/kg and papillary plasma flow increased from 39 to 52 ml/min per 100 g. It is suggested that the natriuretic effect of some vasodilators is due, at least in part, to alterations in medullary hemodynamics, as evidenced by the increase in papillary plasma flow seen with bradykinin and acetylcholine, but not secretin.
Many Pratinidhi Dravyas in Ayurvedic classics are mentioned and certainly are based on a methodical approach, which involves many aspects. These principles on which Pratinidhis were decided are quoted nowhere; so both to understand the established Pratinidhis and to find new ones a rational approach is the need of the hour. This article is an effort in the direction to study this concept meticulously in light of modern techniques for its better understanding and application. As there are very few established parameters, which help for selection and evaluation of Pratinidhi Dravyas. A rational technique like Fourier transform infrared spectroscopy may be incorporated to set a new dimension. As most of the routine analytical techniques are separation based, overall component load cannot be predicted. Thus, it is prime necessity to compare the drugs with a whole aspect, which goes in hand by hand with a holistic approach of Ayurveda “Treat the man as Whole – Take the drug as whole.”
Ayurveda; Fourier transform infrared spectroscopy; Pratinidhi Dravya
The postmenopausal hypoestrogen condition is associated with various lower urinary tract dysfunctions, including frequency, urgency, stress urinary incontinence and recurrent urinary infection. We determined whether hypoestrogen induced lower urinary tract dysfunction after ovariectomy is also associated with an alteration in external urethral sphincter activity.
Materials and Methods
Bilateral ovariectomy was performed in female Sprague-Dawley® rats and sham operated rats served as controls. Transvesical cystometry and external urethral sphincter electromyogram activity were monitored 4, 6 and 12 weeks after sham operation or bilateral ovariectomy and at 6 weeks in bilaterally ovariectomized rats treated with estrogen.
The micturition reflex was elicited in sham operated and bilaterally ovariectomized, urethane anesthetized animals. Post-void residual urine increased and voiding efficiency decreased in rats with 4 to 12 weeks of bilateral ovariectomy. The silent period of external urethral sphincter electromyogram activity was shortened significantly and progressively at increased times after bilateral ovariectomy. These effects were prevented by estradiol treatment.
As evidenced by shortening of the external urethral sphincter electromyogram silent period in ovariectomized rats, the disruption of coordination between the external urethral sphincter and the detrusor muscle could decrease urine outflow and in turn voiding efficiency. Estrogen replacement reverses these changes, suggesting that the central pathways responsible for detrusor-sphincter coordination are modulated by gonadal hormones.
urethra; ovariectomy; estrogens; menopause; urination disorders
A study on the response of the external anal sphincter (EAS) to the passage of urine through the urethra during micturition could not be found in the literature. We investigated the hypothesis that urine passage through the urethra effects EAS contraction to guard against possible flatus or stool leakage during micturition.
The study was performed in 23 healthy volunteers (age, 38.6 ± 10.8 [SD] years; 14 men and 9 women). The EAS electromyogram (EMG) was performed during micturition by surface electrodes applied to the EAS. Also, the EAS EMG response to urethral stimulation by a catheter-mounted electrode was registered. The test was repeated after individual anesthetization of the EAS and urethra.
The EAS EMG recorded a significant increase (P < 0.01) during micturition and on urethral stimulation at the bladder neck. Stimulation of the prostatic, membranous, or penile urethra produced no significant change in the EAS EMG. Urethral stimulation after individual EAS and urethral anesthetization did not cause any changes in the EAS EMG.
Urine passing through the urethra or urethral stimulation at the vesical neck produced an increase in the EAS EMG, which presumably denotes EAS contraction, which seems to guard against flatus or fecal leakage during micturition. EAS contraction on urethral stimulation is suggested to be mediated through a urethro–anal reflex. Further studies on this issue may potentially prove the diagnostic significance of this reflex in micturition and defecation disorders.
Electromyography; Sphincter reflex; Flatus; Stools; Urethra; Defecation; Micturition
Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, increased the urinary excretion of cyclic AMP in normal and parathyroidectomized rats. The increase was greater in rats with intact parathyroid glands than in parathyroidectomized rats. This rise in the urinary excretion of cyclic AMP was not due to an increase in urine flow or a change in urine pH. Furosemide caused an increase in urine flow, but did not affect the excretion of cyclic AMP or phosphate. Alkalinization of the urine with bicarbonate did not increase the urinary excretion of phosphate or cyclic AMP. Acetazolamide increased the productionof cyclic AMP by rat renal cortical slices in vitro. This effect was dose-dependent. Acetazolamide also stimulated the activity of renal cortical adenyl cyclase in a dose-dependent manner but had no effect on the activity of cyclic nucleotide phosphodiesterase. The pattern of urinary excretion of cyclic AMP and phosphate after administration of acetazolamide was similar to that observed in rats given parathyroid hormone. It is suggested that acetazolamide stimulates the renal production of cyclic AMP by activating adenyl cyclase and that this may be the mechanism by which this inhibitor of carbonic anhydrase produces phosphaturia.
Micturition, or urination, occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. The neural circuitry that controls this process is complex and highly distributed: it involves pathways at many levels of the brain, the spinal cord and the peripheral nervous system and is mediated by multiple neurotransmitters. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary or reflex micturition, leading to urinary incontinence. This is a major health problem, especially in those with neurological impairment. Here we review the neural control of micturition and how disruption of this control leads to abnormal storage and release of urine.
The lower urinary tract (LUT) comprises a storage unit, the urinary bladder, and an outlet, the urethra. The coordination between the two structures is tightly controlled by the nervous system and, therefore, LUT function is highly susceptible to injuries to the neuronal pathways involved in micturition control. These injuries may include lesions to the
spinal cord or to nerve fibres and result in micturition dysfunction. A common trait of micturition pathologies, irrespective of its origin, is an upregulation in synthesis and secretion of neurotrophins, most notably Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF). These neurotrophins are produced by neuronal and non-neuronal cells and exert their effects upon binding to their high-affinity receptors abundantly expressed in the neuronal circuits regulating
LUT function. In addition, NGF and BDNF are present in detectable amounts in the urine of patients suffering from various LUT pathologies, suggesting that analysis of urinary NGF and BDNF may serve as likely biomarkers to be studied in tandem with other factors when diagnosing patients. Studies with experimental models of bladder dysfunction
using antagonists of NGF and BDNF receptors as well as scavenging agents suggest that those NTs may be key elements in the pathophysiology of bladder dysfunctions. In addition, available data indicates that NGF and BDNF might constitute future targets for designing new drugs for better treatment of bladder dysfunction.
NGF; BDNF; Trk receptors; bladder; LUT.
The reaction of the corpora cavernosa (CC), the corpus spongiosum (CS), the bulbocavernosus (BCM) and ischiocavernosus (ICM) muscles to passage of urine through the urethra during micturition is not known. We investigated the hypothesis that the passage of urine through the urethra stimulates the corporal tissue and cavernosus muscles.
In 30 healthy men (mean age 42.8 ± 11.7 years), the electromyographic activity (EMG) of the CC, CS, BCM, and ICM were recorded before and during micturition, and on interruption of and straining during micturition. These tests were repeated after individual anesthetization of urethra, corporal tissue, and cavernosus muscles.
During micturition, the slow wave variables (frequency, amplitude, conduction velocity) of the CC and CS decreased while the motor unit action potentials of the BCM and ICM increased; these EMG changes were mild and returned to the basal values on interruption or termination of micturition. Micturition after individual anesthetization of urethra, corporal tissue and cavernosal muscles did not effect significant EMG changes in these structures, while saline administration produced changes similar to those occurring before saline administration.
The decrease of sinusoidal and increase of cavernosus muscles' EMG activity during micturition apparently denotes sinusoidal relaxation and cavernosus muscles contraction. Sinusoidal muscle relaxation and cavernosus muscles contraction upon micturition are suggested to be mediated through a 'urethro-corporocavernosal reflex'. These sinusoidal and cavernosus muscle changes appear to produce a mild degree of penile tumescence and stretch which might assist in urinary flow during micturition.
Santarpanottha Vikaras (diseases due to excessive nutrition) are increasing during current times. Medodushti (disorders of fat metabolism) serves as one of the important etiological factor in most of these disorders including Ischemic Heart Disease (IHD). IHD is identified as one of the leading cause of morbidity and mortality worldwide in both developing and developed countries. Retention and deposition of serum lipids resulting in decreased flow of blood in coronary arteries being the underlying cause. Conventional and herbal drugs are being used to lower levels of serum cholesterol to prevent this menace. In this regard, an attempt has been made to critically review the Medohara and Lekhaniya (Anti-obesity and Hypolipidemic) drugs mentioned in Ganas (group of drugs) of Ayurvedic classical texts which may abet our understanding of prevention and management of conditions like Dyslipidemia and its complications. Administration of drugs possessing Tikta Rasa (bitter taste), Ushna Veerya (hot in potency), Laghu and Ruksha Guna (light and dry qualities), Katu Vipaka and Vata Kaphahara actions were noted during the analysis.
Dyslipidemia; Lekhana; Medohara; obesity; herbs