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1.  Resolvin E2 formation and impact in inflammation-resolution1 
Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized pro-resolving mediators derived from polyunsaturated fatty acids are of interest. Here, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1–10 nM) carries potent leukocyte-directed actions that include 1) regulating chemotaxis of human neutrophils, and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (Kd 24.7 ± 10.1 nM) and RvE1 activation of recombinant GPCRs was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.
PMCID: PMC3331964  PMID: 22450811
Experimental cell research  2010;316(10):1706-1715.
12-lipoxygenase, an arachidonic acid metabolizing enzyme of the lipoxygenase pathway, has been implicated as a major factor in promoting prostate cancer progression and metastasis. The ability of 12-LOX to aggravate the disease was linked to its proangiogenic role. Recent studies clearly demonstrated that 12-LOX enhances the expression and secretion of the angiogenic factor, vascular endothelial growth factor (VEGF) thus providing a direct link between this enzyme and its angiogenic properties. In the present study we have investigated the relationship between 12-LOX and hypoxia inducible factor-1α (HIF-1α), a transcription factor involved in the regulation of VEGF expression under hypoxic conditions in solid tumors. Our findings have revealed that HIF-1 is one of the target transcription factors regulated by 12-LOX and 12(S)-HETE, in hypoxic tumor cells of the prostate. Regulation of HIF-1α by 12-LOX adds to the complexity of pathways mediated by this enzyme in promoting prostate cancer angiogenesis and metastasis. We have evidence that 12-LOX increases the protein level, mRNA, and functional activity of HIF-1α under hypoxic conditions, one of the mechanisms by which it upregulates VEGF secretion and activity.
PMCID: PMC3420817  PMID: 20303950
12-Lipoxygenase; Hypoxia Inducible Factor-1α (HIF-1α); angiogenesis; prostate cancer; hypoxia
3.  Novel Anti-Inflammatory -- Pro-Resolving Mediators and Their Receptors 
Resolution of inflammation, an actively coordinated program, is essential to maintain host health. It involves effective removal of inflammatory stimuli and the spatio-temporal control of leukocyte trafficking as well as chemical mediator generation. During the active resolution process, new classes of small, local acting endogenous autacoids, namely the lipoxins, D and E series resolvins, (neuro)protectins, and maresins have been identified. These specialized pro-resolving lipid mediators (SPM) prevent excessive inflammation and promote removal of microbes and apoptotic cells, thereby expediting resolution and return to tissue homeostasis. As part of their molecular mechanism, SPM exert their potent actions via activating specific pro-resolving G-protein coupled receptors. Together these SPM and their receptors provide new concepts and opportunities for therapeutics, namely promoting active resolution as opposed to the conventionally used enzyme inhibitors and receptor antagonists. This approach may offer new targets suitable for drug design for treating inflammation related diseases, for the new terrain of resolution pharmacology.
PMCID: PMC3094721  PMID: 21261595
G-protein coupled receptor; inflammatory exudates; leukocytes; mediator lipidomics; omega-3 fatty acids; resolvins
5.  Isolated tuberculous orchitis: A mimicker of testicular malignancy 
Isolated tuberculous orchitis is a rare entity. The coexistence of tuberculosis of the testis with filarial worm infestation is even more rare. In this report, we present a case of tuberculous involvement of the testis, associated with filarial worm infestation in the spermatic cord that presented as a testicular tumor. A 55-year-old male presented with unilateral testicular swelling of four months duration. As the clinical evaluation was suggestive of testicular malignancy, he underwent a right high orchidectomy. The histopathology report revealed isolated tuberculous orchitis without epididymal involvement along with filarial infestation of the spermatic cord.
PMCID: PMC2938556  PMID: 20877610
Filariasis; testicular tumor; tuberculous orchitis
6.  Hematuria: An uncommon presentation of Glanzmann's thrombasthenia—Lessons learnt 
A 55-year-old man with Glanzmann's thrombasthenia had recurrent episodes of gross painless hematuria for the past 30 years. His last episode of hematuria occurred a month ago, associated with pain in the right loin and was diagnosed to have a right mid-ureteric calculus. Under adequate platelet cover, he underwent right ureteroscopy. Postoperatively, he had persistent significant hematuria that did not improve despite repeated platelet transfusions. Factor VIIa was also transfused, without much benefit. A ureteroscopy was done, which identified bleeding from within the renal pelvis. CT angiogram confirmed the rupture of an artery supplying the interpole segment of the right kidney. Bleeding settled after angioembolization. Indiscriminate use of platelet transfusions would result in a state of platelet refractoriness. It is also important to suspect an iatrogenic cause for any complication that occurs after a surgical procedure, even if there could be an underlying medical etiology that can be attributed to the development of such complication.
PMCID: PMC2878421  PMID: 20535297
Glanzmann's thrombasthenia; hematuria; platelet transfusions
7.  Detrusor underactivity: To tone or not to tone the bladder? 
The aim of this review was to review the available evidence in literature for the clinical effectiveness of Bethanechol Chloride in patients with detrusor underactivity.
Materials & Methods:
We searched all relevant data from Medline and peer-reviewed journals available online on the use of bethanechol in patients with detrusor underactivity.
Most reports that suggest a therapeutic clinical benefit with use of bethanechol have all been anecdotal reports and there is no definite clinical evidence available till date to support its clinical usefulness.
The current available data have shown to offer no definite benefit with the use of parasympathomimetic agents in patients with DU. One of the meta-analysis has shown bethanechol to be ineffective in promoting bladder emptying.
PMCID: PMC2779972  PMID: 19881143
Detrusor underactivity; Bethanechol chloride; parasympathomimetics
8.  Detection and treatment of transplant renal artery stenosis 
To assess the effects of transplant renal artery stenosis (TRAS) on blood pressure, renal function, and graft survival. To assess the usefulness of Doppler in predicting the clinical significance of TRAS and also to identify the predictive factors in Doppler that correlated with clinical features of TRAS.
Materials and Methods:
A prospective study was done on consecutive renal allograft recipients at Christian Medical College, over a period of 66 months from January 2002. All recipients underwent Doppler ultrasound (DUS) evaluation on the fifth post-operative day. Subsequent evaluation was done if the patients had any clinical or biochemical suspicion of TRAS. Angiogram was done in case of a high index of suspicion of significant stenosis or before angioplasty and stenting. The clinical and radiological outcomes of the patients with symptomatic or asymptomatic TRAS were analyzed.
Five hundred and forty three consecutive renal allograft recipients were analyzed, of whom, 43 were found to have TRAS. Nine recipients (21%) were detected to have TRAS on first evaluation. All had a high peak systolic velocities (PSV) recorded while 25 of them had other associated features. Patients with only high PSV required no further intervention and were followed up. They had a pretransplant mean arterial pressure (MAP) of 107.83 mmHg (SD = 13.32), ranging from 90 to 133 mm Hg and a posttransplant MAP of 106.56 mmHg (SD =16.51), ranging from 83 to 150 mm Hg. Their mean nadir serum creatinine was 1.16 mg% (SD = 0.24), at detection was 1.6 mg% (SD = 1.84) and at 6 months follow-up was 1.26 mg% (SD=0.52). Of the remaining 25 patients with other associated Doppler abnormalities, 11 required further intervention in the form of re-exploration in 2, angioplasty in 3 and stenting in 6 patients. One patient in the group of patients intervened, expired in the immediate post-operative period due to overwhelming urosepsis and consumption coagulopathy. The mean creatinine clearance (Cockroft-Gault method) in this group of remaining 10 patients, before and after intervention was 44.75 ml/min (SD=17.85) and 68.96 ml/min (SD = 10.56), respectively, with a mean increase by 24.21 ml/min (P=0.000). The mean arterial pressure before and after intervention in this group were 132.80 mm Hg (SD = 13.22) and 102 mm Hg (SD = 10.55), with a decline in the MAP by 30.80 mmHg (P=0.017). The haemoglobin levels also increased from 11.72 (SD=2.13) to 12.48 gm% (SD = 1.75), with a mean increase by 0.76 gm% (P=0.05).
Patients with isolated high PSV do not have a significant alteration of blood pressure or allograft function and required no intervention. Although high PSV with associated Doppler anomalies are more suggestive of significant TRAS, the decision regarding surgical intervention is largely based on clinical assessment.
PMCID: PMC2684311  PMID: 19468430
Angioplasty; peak systolic velocity; transplant renal artery stenosis
9.  Surgical management of renal tuberculosis 
Tuberculosis (TB) is one of the major health problems that our country is facing today. Despite active interventions by our government, control of TB still remains to be achieved. The emergence and exponential growth of the human immunodeficiency virus and drug-resistant strains threaten to further complicate the TB situation in our country. Even in this era of advanced chemotherapy, many lives are lost every day in our country. Tuberculosis of the urinary tract, despite being one of the commonest forms of extra-pulmonary TB, is generally overlooked. Most patients present with vague lower urinary symptoms typical of urinary tract infection. In this article, we shall highlight the various issues related to the surgical management of renal and ureteral tuberculosis.
PMCID: PMC2684360  PMID: 19468471
Hydronephrosis; nephrectomy; renal tuberculosis

Results 1-9 (9)