Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.
diabetic neuropathy; nicotinamide-streptozotocin; metformin; pioglitazone; glimipiride; sitagliptin; amitriptyline
The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.
Allium sativum Linn.; ischemic preconditioning; cardioprotection; adenosine; nitrite
Multiplex Polymerase Chain Reaction (MPCR) is a technique in which two or more gene targets are amplified in a single reaction. This has increased sensitivity of diagnosis as a single gene target may be absent in some Mycobacterium tuberculosis strains.
MPCR using two target genes specific for Mycobacterium tuberculosis, that is, IS6110 and MPB 64, ZN staining and Mycobacterial culture were performed on synovial fluid/pus samples of 80 (three confirmed, 77 suspected) patients of osteoarticular tuberculosis and 25 non tuberculosis patients.
MPCR had a sensitivity of 100% in confirmed cases and 81.8% in clinically suspected cases. AFB was positive in one patient and Mycobacterial culture was positive in three patients. MPCR also had 100% specificity; MPB64 was positive in five patients in which IS6110 was negative whereas IS6110 was positive in two patients in which MPB64 was negative.
MPCR is a sensitive and specific method for diagnosis of paucibacilliary conditions such as osteoarticular tuberculosis.
Four strains (NL-1, NL-1n, NL-7 and NL-7n) of Bean common mosaic virus (BCMV) prevalent on common bean (Phaseolus vulgaris) in Himachal Pradesh, a north-western Himalayan state of India were compared at the 3′ terminal region of the viral genome to elucidate variation and relationship among these strains. 3′ terminal region comprising of partial nuclear inclusion b (NIb) (171–233 bp), complete coat protein (CP) (860 bp) and 3′ untranslated region (UTR) (208–244 bp) shared 96–98% nucleotide and 96–99% amino acids identity among various strains of BCMV. Multiple alignment as well as cluster dendrograms of the 3′ terminal region placed the test isolates in BCMV species of genus Potyvirus. Phylogenetic analysis of complete CP as well as 3′ UTR also showed Indian strains to be distinct strains. Sequence homology, multiple alignment and evolutionary divergence of 3′ terminal region could not differentiate the pathogenic strain groups, thereby establishing least role of this region in strain characterization of the virus. Comparisons of CP and 3′ UTR region of BCMV strains and other members of genus Potyvirus clearly indicated the little utility of 3′ terminal region in distinction of virus strains. Implications of coat protein region in viral strain distinction are also discussed.
BCMV; Common bean; Strains; Coat protein; Variability
Some new compounds of aluminium having the general formula AI[SC6H4N:C(R) CH2 C(O)R’]3 where R = CH3, R' = CH3 (1); R' = CH3, R' = C6H5 (2); R = CF3, R’ = -C = CH - CH = CHS (3); R = CF3, R’ = C6H5 (4) have been synthesised by the reactions of Al(OPri)3 and the corresponding ligands in 1:3 molar ratios in benzene. Elemental and spectroscopic (IR, 1H, 13C, and 27AI NMR) characterisation of these monomeric compounds reveals monofunctional bidentate behaviour of ligand moiety and the octahedral geometry around
aluminium atom. Compound (1), AI[SC6H4N:C(CH3)CH2COCH3], has been tested for its antifertility activity in male albino rats. The oral administration of this compound at the dose level 6.5 rag/rat/day reduced the
weights of testes and epididymides. Significant decrease in sperm motility as well as sperm density resulted
in the reduction of male fertility by 100%. Production of primary spermatocytes (preleptotene and
pachytene), secondary spermatocytes and step-19 spermatids declined by 56.10%, 44.42 %, 63.35 % and
64.57 % respectively. These results indicate that the administration of compound (1) in male rats brought
about an interference with spermatogenesis which ultimately caused infertility.
Plants by virtue of its composition of containing multiple constituents developed during its growth under various environmental stresses providing a plethora of chemical families with medicinal utility. Researchers are exploring this wealth and trying to decode its utility for enhancing health standards of human beings. Diabetes is dreadful lifestyle disorder of 21st century caused due to lack of insulin production or insulin physiological unresponsiveness. The chronic impact of untreated diabetes significantly affects vital organs. The allopathic medicines have five classes of drugs, or otherwise insulin in Type I diabetes, targeting insulin secretion, decreasing effect of glucagon, sensitization of receptors for enhanced glucose uptake etc. In addition, diet management, increased food fiber intake, Resistant Starch intake and routine exercise aid in managing such dangerous metabolic disorder. One of the key factors that limit commercial utility of herbal drugs is standardization. Standardization poses numerous challenges related to marker identification, active principle(s), lack of defined regulations, non-availability of universally acceptable technical standards for testing and implementation of quality control/safety standard (toxicological testing). The present study proposed an integrated herbal drug development & standardization model which is an amalgamation of Classical Approach of Ayurvedic Therapeutics, Reverse Pharmacological Approach based on Observational Therapeutics, Technical Standards for complete product cycle, Chemi-informatics, Herbal Qualitative Structure Activity Relationship and Pharmacophore modeling and, Post-Launch Market Analysis. Further studies are warranted to ensure that an effective herbal drug standardization methodology will be developed, backed by a regulatory standard guide the future research endeavors in more focused manner.
Diabetes; Standardisation; Herbal drugs; Drug development
Unlike somatic cells, sperm have several-fold more available-thiols that are susceptible to redox-active agents. The present study explains the mechanism behind the instant sperm-immobilizing and trichomonacidal activities of pyrrolidinium pyrrolidine-1-carbodithioate (PPC), a novel thiol agent rationally created for prophylactic contraception by minor chemical modifications of some known thiol drugs. PPC, and its three derivatives (with potential active-site blocked by alkylation), were synthesized and evaluated against live human sperm and metronidazole-susceptible and resistant Trichomonas vaginalis, in vitro. Sperm hexokinase activity was evaluated by coupled enzyme assay. PPC irreversibly immobilized 100% human sperm in ∼30 seconds and totally eliminated Trichomonas vaginalis more efficiently than nonoxynol-9 and metronidazole. It significantly inhibited (P<0.001) thiol-sensitive sperm hexokinase. However, the molecule completely lost all its biological activities once its thiol group was blocked by alkylation. PPC was subsequently formulated into a mucoadhesive vaginal film using GRaS excipients and evaluated for spermicidal and microbicidal activities (in vitro), and contraceptive efficacy in rabbits. PPC remained fully active in quick-dissolving, mucoadhesive vaginal-film formulation, and these PPC-films significantly reduced pregnancy and fertility rates in rabbits. The films released ∼90% of PPC in simulated vaginal fluid (pH 4.2) at 37°C in 5 minutes, in vitro. We have thus discovered a common target (reactive thiols) on chiefly-anaerobic, redox-sensitive cells like sperm and Trichomonas, which is susceptible to designed chemical interference for prophylactic contraception. The active thiol in PPC inactivates sperm and Trichomonas via interference with crucial sulfhydryl-disulfide based reactions, e.g. hexokinase activation in human sperm. In comparison to non-specific surfactant action of OTC spermicide nonoxynol-9, the action of thiol-active PPC is apparently much more specific, potent and safe. PPC presents a proof-of-concept for prophylactic contraception via manipulation of thiols in vagina for selective targeting of sperm and Trichomonas, and qualifies as a promising lead for the development of dually protective vaginal-contraceptive.
Rapid and specific diagnosis of gastrointestinal tuberculosis (GITB) is of utmost importance.
To evaluate Multiplex PCR (MPCR) using MPB64 and IS6110 primers specific for M. tuberculosis for rapid diagnosis of GITB.
Materials and Methods:
MPCR was performed on colonoscopy biopsy specimens on 11 GITB confirmed (culture/AFB/histopathology was positive), 29 GITB suspected and 30 Non GITB (control group) patients.
MPB64 PCR had sensitivity and specificity of 90% and 100% for confirmed GITB cases. In 29 clinically diagnosed but unconfirmed GITB cases, MPCR was positive in 72.41%. MPCR was negative in all control group patients. The overall sensitivity and specificity of microscopy, culture, histopathology and MPCR was 5%, 2% 20% and 77.5% and 100%, 100%, 100% and 100% respectively.
MPCR has good sensitivity and specificity in diagnosing gastrointestinal tuberculosis.
Gastrointestinal tract; Multiplex PCR; Tuberculosis
The objective of this study was to report the use of multi-targeted polymerase chain reaction (PCR) in the diagnosis of presumed tubercular uveitis. Multi-targeted PCR using three targets specific for Mycobacterium tuberculosis, i.e., IS6110, MPB64, and protein b, was performed on intraocular fluid samples of 25 subjects. Nine had presumed tubercular uveitis, six had intraocular inflammation secondary to a nontubercular etiology (disease controls), and ten had no evidence of intraocular inflammation (normal controls). As described previously, response to antitubercular therapy was considered as the gold standard.
Multi-targeted PCR was positive in seven out of nine patients with presumed tubercular uveitis and negative in all normal and disease controls. The sensitivity and specificity were 77.77% and 100%, respectively. For the diagnosis of presumed tubercular uveitis, multi-targeted PCR had a positive predictive value of 100% and a negative predictive value of 88.88%.
Multi-targeted PCR can be a valuable tool for diagnosing presumed tubercular uveitis.
Uveitis; Tubercular; Polymerase chain reaction; Multi-targeted PCR
To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before orthopaedic surgery.
Materials and Methods:
We conducted a randomized controlled trial of recombinant human erythropoietin in 68 adults scheduled for elective orthopedic procedures. The patients received either erythropoietin 600 units/kg of body weight or placebo intravenously every 5th day prior to each phlebotomy for 21 days during which time up to 5 units of blood was collected. Patients were excluded from donation when their hematocrit values were less than 33%. All patients received iron sulphate 325mg orally 3 times daily. The mean number of units collected per patient was 4.33 ± 0.4 for erythropoietin group and 3.05± 0.71 for the placebo group.
The mean packed red cell volume donated by patients who received erythropoietin was 32% greater than that donated by patients who received placebo (196.3 vs. 169.4 ml, p<0.05). 68% in the placebo group and 9% of patients treated with erythropoietin were unable to donate ≥4 units. No adverse effects were attributed to erythropoietin. While participating in the study, complications developed in 2 patients one in each group necessitating their removal from the study.
We conclude that recombinant human erythropoietin increases the ability of the patients about to undergo elective surgery to donate autologous blood units.
Autologous blood; preoperative; recombinant human erythropoietin
Paraneoplastic pemphigus (PNP), a clinically and immunopathologically distinct mucocutaneous blistering dermatosis, is a severe form of autoimmune multiorgan syndrome generally associated with poor therapeutic outcome and high mortality. This IgG-mediated disease is initiated by an obvious or occult lymphoproliferative disorder in most cases. Clinically severe mucositis, and polymorphic blistering skin eruptions, and histologically acantholysis, keratinocyte necrosis and interface dermatitis are its hallmark features. A 58-year-old female presented with recurrent, severe, recalcitrant stomatitis and widespread erosions/blistering lesions of one-year duration. Treatment with repeated courses of systemic corticosteroids at a peripheral center would provide temporary relief. She also had fever, productive cough, odynophagia and poor oral intake, herpes zoster ophthalmicus, pain in the abdomen, and watery diarrhea. An array of investigations revealed chronic lymphocytic leukemia (CLL), mediastinal and para-aortic lymphadenopathy, bronchiolitis obliterans, and vertebral osteoporosis/fractures. With the diagnosis of CLL-associated PNP she was managed with dexamethasone-cyclophosphamide pulse (DCP) therapy for 3 cycles initially, followed by COP regimen (cyclophosphamide, vincristine, and prednisolone) for 5 cycles. Remission is being maintained with chlorambucil and prednisolone pulse therapy once in 3 weeks with complete resolution of skin lesions and adequate control of CLL.
Basal cell carcinoma (BCC) accounts for 80% of all nonmelanoma skin cancers. Its metastasis is extremely rare, ranging between 0.0028 and 0.55 of all BCC cases. The usual metastasis to lymph nodes, lungs, bones, or skin is from the primary tumor situated in the head and neck region in nearly 85% cases. A 69-year-old male developed progressively increasing multiple, fleshy, indurated, and at places pigmented noduloulcerative plaques over back, chest, and left axillary area 4 years after wide surgical excision of a pathologically diagnosed basal cell carcinoma. The recurrence was diagnosed as infiltrative BCC and found metastasizing to skin, soft tissue and muscles, and pretracheal and axillary lymph nodes. Three cycles of chemotherapy comprising intravenous cisplatin (50 mg) and 5-florouracil (5-FU, 750 mg) on 2 consecutive days and repeated at every 21 days were effective. As it remains unclear whether metastatic BCC is itself a separate subset of basal cell carcinoma, we feel that early BCC localized at any site perhaps constitutes a biological continuum that may ultimately manifest with metastasis in some individuals and should be evaluated as such. Long-standing BCC is itself potentially at risk of recurrence/dissemination; it is imperative to diagnose and appropriately treat all BCC lesions at the earliest.
Congenital insensitivity to pain with anhidrosis is an extremely rare disorder in which injuries can often be missed by patient, parents and even by orthopedic surgeon. Pain and tenderness, on which a trauma team so much depends to make a clinical diagnosis and to decide whether to go for radiological evaluation can be misleading in this rare syndrome. So complete clinical examination still forms the corner stone to avoid misdiagnosis and pick up the rare disorders.
We present a 5 year old girl child, who was brought to us as a case of one and a half month old neglected trauma left leg and was diagnosed to be suffering from congenital insensitivity to pain with anhidrosis (HSAN Type IV).
Congenital insensitivity to pain with anhidrosis is extremely rare entity, in which patients are subjected to repeated injuries which are often neglected. There is no specific treatment but patient training and parent education are key to avoid further neglect and damage.
Congenital Insensitivity to Pain with Anhidrosis; Hereditary sensory autonomic neuropathy; Anhidrosis; Osteoacrolysis; Hyperpyrexia
To compare the efficacy of gatifloxacin, azithromycin with amoxicillin as positive control for the treatment of Acute rhinosinusitis (ARS). To monitor adverse drug reaction profile of amoxicillin, azithromycin and gatifloxacin in patient of ARS. An open randomized trial of comparative efficacy and safety of amoxicillin, azithromycin and gatifloxacin in patients with ARS. Patients were randomized into three groups as under: group 1: patients on oral amoxicillin 500 mg TDS for 10 days; group 2: patients on oral azithromycin 500 mg OD for 5 days; group 3: patients on oral gatifloxacin 400 mg OD for 10 days. Patients were evaluated for signs and symptoms at day 1, day 7 (for group 2), on day 12 (for group 1, 3) as primary end points and 28 days after post therapy as secondary end point. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Azithromycin showed significant improvement radiographically on day 7 (P < 0.01) and on day 35 (P < 0.01). Gatifloxacin elicited very highly significant improvement radiographically on day 40 (P < 0.001) and significant improvement on day 12 (P < 0.01) when compared with amoxicillin. Azithromycin, the ketolide was associated with lesser adverse effects as compared to amoxicillin. All the three antimicrobial drugs i.e., amoxicillin, azithromycin and gatifloxacin were effective in reducing symptoms of acute sinusitis on visual analogue scale scoring. Gatifloxacin was found to be most effective drug both in terms of improvement in signs and symptoms on visual analogue scale and radiographic scoring and was associated with least adverse events in comparison to rest of two drugs under study.
Acute rhinosinusitis (ARS); Gatifloxacin-respiratory fluoroquinolone, ketolide-azithromycin; Aminopenicillin-amoxicillin
In this part importace and specialize of sushruta are specified. In Part – 1 all the translation works in all the available languages is narrated. After studying all those books and keeping in to mind about a comprehensive work of sushruta it is necessary to elaborate in this present text. This part is divided into 5 sections. (A) All available commentaries taken in to consideration for this part is written, (B) Specialities of sushruta are most important as he has narrated all eight sections of Ayurveda elabroted widely where as caraka has only narrated mainly selected part of kAya-cikitsA and left other sections for other authors e.g., “atra dhAnavantareyaNAM adhikArah” etc., Specifying a list of all sections and chapters with the numbers of prose + poetery, (C) None of the translator or commentator touched the importance of sushruta in the literature of samskRta, where as sushruta was a great poet. Giving similar resemblance of common use by mass, he tried to explain the tough subject in simpler mode of knowledge for proper understanding to all public. He has specifically selected the prosody for the specified subject. Examples are given in this section. (D) sushruta has written prosody in14 metres and long sentences too in samskRta that shows his ability and wast knowledge in the literature. All references of each and every metre is noted from all sections of sushruta with complete reference numbers. And no where this subject is published till now- (E) A challenging word regarding the work of sushruta “shArIre sushruto naSTah” is turned back while quoting various references of shArIra-sthAnam and placing its world wide importance by various writers.
Ayurveda; caraka; sushruta; sushruta samhitA
Gastrointestinal involvement is common in patients of human immunodeficiency virus infection (HIV) and the acquired immunodeficiency syndrome (AIDS). Specific gastrointestinal disorders often correlate with degree of immunosuppression. In advance cases of HIV infection GI symptoms are usually part of systemic infection. In such scenario multiple infections are common so failure to diagnose a specific cause is not uncommon. We here present a case study of a patient with ileal perforation with tubercular etiology and its management
AIDS; Ileal perforation; tuberculosis
In the history of Ayurveda, Sushruta stands before Caraka. He practically applied Vaidika culture for treatment. His treatise translated into nine foreign languages apart from various Indian languages like Hindi, Bengali, Malayalam, etc., Sushruta is the most celebrated physician and surgeon in India. Though he practiced during the 5th century BC, many of his contributions to medicine and surgery preceded similar discoveries in the western world. Sushruta devotes a complete volume of his experiences to ophthalmologic diseases. In the Uttara Tantram, Sushruta enumerates a sophisticated classification of eye diseases complete with signs, symptoms, prognosis, and medical/surgical interventions. In particular, Sushruta describes what may have been the first extracapsular cataract surgery using a sharply pointed instrument with a handle fashioned into a trough. His ability to manage many common eye conditions of the time with limited diagnostic aids is a testament to his virtuosity.
Ayurveda; Caraka; Sushruta; Sushruta Samhita
Background & objectives:
The bottle gourd (Lagenaria siceraria) is popularly known as lauki, ghia or dudhi in India. Its consumption is advocated by traditional healers for controlling diabetes mellitus, hypertension, liver diseases, weight loss and other associated benefits. However, in last few years there have been reports of suspected toxicity due to consumption of its juice. This led to the constitution of an Expert Committee by Department of Health Research at Indian Council of Medical Research (ICMR), Ministry of Health & Family Welfare, Government of India in October 2010. The committee looked into the issues related to safety of consumption of bottle gourd juice, and this paper presents the findings.
Information on cases of suspected toxicity due to consumption of bottle gourd juice was collected by internet search, advertising on website of ICMR and by writing to State and district health authorities as well as to medical colleges, hospitals and private nursing homes across the country.
Three deaths were reported, one from Delhi and two from Uttar Pradesh after consumption of extremely bitter bottle gourd juice. Three persons who died after consumption of freshly prepared bottle gourd juice or juice mixed with bitter gourd (karela) juice were over 59 years of age and had diabetes since last 20 years. This juice was reported to be extremely bitter by all three. Twenty six persons were admitted to various hospitals of the country on complaint of abdominal pain and vomiting following consumption of freshly prepared bottle gourd juice. Diarrhoea and vomiting of blood (haematemesis) was reported in 18 (69.2%) and 19 (73.1%) patients, respectively. Biochemical investigations revealed elevated levels of liver enzymes. More than 50 per cent patients had hypotension. Endoscopic findings showed profusely bleeding stomach with excessive ulceration seen in distal oesophagus, stomach and duodenum in most of the cases. All these patients recovered fully and no sequeale was recorded for any of the cases.
Interpretation & conclusions:
Cucurbitaceae family, of which bottle gourd is a member contains the toxic tetracyclic triterpenoid compounds called cucurbitacins which are responsible for the bitter taste. There is no known antidote for this toxicity and clinicians treat such cases symptomatically only. The Committee made the following recommendations: (i) The community needs to be educated that bitter tasting bottle gourd juice should not be consumed and in case there is any discomfort, nausea, vomiting, diarrhoea or any feeling of uneasiness after consumption of juice, the person should immediately be taken to a nearby hospital. (ii) Clinicians are suggested that patients coming with symptoms (discomfort, nausea, vomiting, diarrhoea, gastrointestinal bleeding after consumption of juice) should immediately be attended to and general supportive care should be provided, i.e. IV fluids/crystalloids/blood products/fresh frozen plasma to maintain the haemodynamics and electrolyte balance; Ryle's tube to be put in for gastric lavage and to assess gastrointestinal (GI) bleed- aspirate to be preserved; Proton pump inhibitors should be given for management of GI bleed and appropriate treatment for other complications should be given. (iii) The possible research areas identified are chemical composition studies on bitter and normal bottle gourd and other members of cucurbitaceae family; animal toxicity studies and studies on interaction between bottle gourd juice and other drugs.
Bitter taste; bottle gourd; calabash; cucurbitacins; juice; Lagenaria sicraria; toxicity
Accuracy of aminoacylation is dependent on maintaining fidelity during attachment of amino acids to cognate tRNAs. Cis- and trans-editing protein factors impose quality control during protein translation, and 8 of 36 Plasmodium falciparum aminoacyl-tRNA synthetase (aaRS) assemblies contain canonical putative editing modules. Based on expression and localization profiles of these 8 aaRSs, we propose an asymmetric distribution between the parasite cytoplasm and its apicoplast of putative editing-domain containing aaRSs. We also show that the single copy alanyl- and threonyl-tRNA synthetases are dually targeted to parasite cytoplasm and apicoplast. This bipolar presence of two unique synthetases presents opportunity for inhibitor targeting their aminoacylation and editing activities in twin parasite compartments. We used this approach to identify specific inhibitors against the alanyl- and threonyl-tRNA synthetases. Further development of such inhibitors may lead to anti-parasitics which simultaneously block protein translation in two key parasite organelles, a strategy of wider applicability for pathogen control.
Thioredoxins are vital components of Plasmodium proteome and act as both reducing
agents and protein disulfide reductases. The malaria parasite P. falciparum
thioredoxin-2 (PfTrx-2) is part of the multi-protein complex embedded within the parasite
parasitophorous vacuolar membrane (PVM) which purportedly directs protein secretion. We have
characterized structural and enzymatic features of PfTrx-2, and we show that PfTrx-2 adopts
a canonical thioredoxin fold but with significant structural differences in its N-terminus.
Our confocal localization data suggest distinct PVM residency of PfTrx-2. Based on the
crystal structure of PfTrx-2, we screened and tested small molecule drug-like libraries for
compounds which target unique structural features of PfTrx-2. Disruption of PfTrx-2
interactions using specific inhibitors may result in a dysfunctional parasite translocon
that is rendered unable to secrete pathogenic proteins into hosts. This approach therefore
offers a new focus for anti-malarial drug development.
The region around Chandigarh in India has witnessed a resurgence of cholera. However, isolation of V. cholerae O1 from the environment is infrequent. Therefore, to study whether environmental nonO1-nonO139 isolates, which are native to the aquatic ecosystem, act as precursors for pathogenic O1 strains, their virulence potential and evolutionary relatedness was checked.
V. cholerae was isolated from clinical cases of cholera and from water and plankton samples collected from freshwater bodies and cholera-affected areas. PCR analysis for the ctxA, ctxB, tcpA, toxT and toxR genes and AFLP with six primer combinations was performed on 52 isolates (13 clinical, 34 environmental and 5 reference strains).
All clinical and 3 environmental isolates belonged to serogroup O1 and remaining 31 environmental V. cholerae were nonO1-nonO139. Serogroup O1 isolates were ctxA, tcpA (ElTor), ctxB (Classical), toxR and toxT positive. NonO1-nonO139 isolates possessed toxR, but lacked ctxA and ctxB; only one isolate was positive for toxT and tcpA. Using AFLP, 2.08% of the V. cholerae genome was interrogated. Dendrogram analysis showed one large heterogeneous clade (n = 41), with two compact and distinct subclades (1a and 1b), and six small mono-phyletic groups. Although V. cholerae O1 isolates formed a distinct compact subclade, they were not clonal. A clinical O1 strain clustered with the nonO1-nonO139 isolates; one strain exhibited 70% similarity to the Classical control strain, and all O1 strains possessed an ElTor variant-specific fragment identified with primer ECMT. Few nonO1-nonO139 isolates from widely separated geographical locations intermingled together. Three environmental O1 isolates exhibited similar profiles to clinical O1 isolates.
In a unique study from freshwater environs of a cholera-endemic area in India over a narrow time frame, environmental V. cholerae population was found to be highly heterogeneous, diverse and devoid of major virulence genes. O1 and nonO1-nonO139 isolates showed distinct lineages. Clinical isolates were not clonal but were closely related, indicating accumulation of genetic differences over a short time span. Though, environment plays an important role in the spread of cholera, the possibility of an origin of pathogenic O1 strains from environmental nonO1-nonO139 strains seems to be remote in our region.
The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia (T. cordifolia) in CaCl2 induced arrhythmia. CaCl2 (25 mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract (150, 250, and 450 mg/kg) and verapamil (5 mg/kg,iv). Lead II electrocardiogram was monitored. Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and 450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively, and verapamil reduced the heart rate by 9.70% compared to the normal group. The PQRST waves were normalized and atrial and ventricular fibrillation was controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased calcium and sodium levels and decreased potassium levels in blood. T. cordifolia dose-dependently decreased calcium and sodium levels and increased potassium levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and beneficial in atrial and ventricular fibrillation and flutter and may be indicated in ventricular tachyarrhythmia.
Tinospora cordifolia; arrhythmia; cardioprotection.