Aaditya Tarnekar

Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium-induced colitis in mice.

Helminth immunomodulation in the host has been shown to have therapeutic implications in inflammatory bowel diseases. In this study we aimed to evaluate the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in a dose‐dependent manner on dextran sulfate sodium (DSS)‐induced colitis in mice.

Brugia malayi soluble and excretory-secretory proteins attenuate development of streptozotocin-induced type 1 diabetes in mice

Understanding the modulation of the host‐immune system by pathogens‐like filarial parasites offers an alternate approach to prevent autoimmune diseases. In this study, we have shown that treatment with filarial proteins prior to or after the clinical onset of streptozotocin‐induced type‐1 diabetes (T1D) can ameliorate the severity of disease in BALB/c mice. Pre‐treatment with Brugia malayi adult soluble (Bm A S) or microfilarial excretory‐secretory (Bm mf ES) or microfilarial soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of fasting blood glucose levels with as many as 57·5–62·5% of mice remaining nondiabetic. These proteins were more effective when they were used to treat the mice with established T1D as 62·5–71·5% of the mice turned to be nondiabetic. Histopathological examination of pancreas of treated mice showed minor inflammatory changes in pancreatic islet cell architecture. The therapeutic effect was found to be associated with the decreased production of cytokines TNF‐α & IFN‐γ and increased production of IL‐10 in the culture supernatants of splenocytes of treated mice. A switch in the production of anti‐insulin antibodies from IgG2a to IgG1 isotype was also seen. Together these results provide a proof towards utilizing the filarial derived proteins as novel anti‐diabetic therapeutics.

Prevalence of Y Chromosome Microdeletions in Idiopathic Azoospermia Cases in Central Indian Men.

BACKGROUND Genetic factor is important determinant of human male fertility, it is involved in 10-15% infertile males. Chromosome abnormalities and Y chromosome microdeletions are the main genetic causative factors for infertility. The frequency of male infertility & microdeletions in Y chromosome are also related to ethnic, geographical variations. In this study, we evaluated the prevalence of chromosomal abnormalities and microdeletions of Y chromosome in infertile azoospermia cases in central India to assess the geographical or population based variations. MATERIALS AND METHODS We have studied 160 non-obstructive azoospermia cases to find out frequency of chromosomal abnormalities and Y chromosome microdeletions of AZF locus. G-banding method was used for exclusion of chromosomal abnormalities. One hundred and forty eight azoospermic infertile men were screened using 12 sequence-tagged-sites (STS) primers of AZFa, AZFb, AZFc region and SRY gene (Yp) region by polymerase chain reactions. RESULTS Out of 160 azoospermic infertile males, 12 (7.5%) confirmed chromosomal abnormalities and Klinefelters syndrome was predominantly cause of azoospermia. Of the 148 infertile males, 19 (12.8%) were shown microdeletions in different AZF regions. Deletions in AZFa region were 2.02% and 3.37% was in AZFb whereas high frequencies of deletions (6.08%) in AZFc were recorded in azoospermic males. In two azoospermic males were shown microdeletions in AZFb+c loci. CONCLUSION The prevalence of Y chromosome microdeletions in azoospermic men was 12.8% in this geographical region. Klinefelters syndrome is important cause in male infertility. So, the screening of Y microdeletions is essential.

Large Scale 7436-bp Deletions in Human Sperm Mitochondrial DNA with Spermatozoa Dysfunction and Male Infertility

INTRODUCTION Mitochondria and mitochondrial DNA are essential to sperm motility and fertility. It controls growth, development and differentiation through oxidation energy supply. Mitochondrial (mtDNA) deletions or mutation are frequently attributed to defects of sperm motility and finally these deletions lead to sperm dysfunction and causes infertility in male. AIM To investigate the correlation between large scale 7436-bp deletions in sperm mtDNA and non-motility of sperm in asthenozoospermia and Oligoasthenoteratozoospermia (OAT) infertile men. MATERIALS AND METHODS The present prospective study was carried out in Human Genetic Division, Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram from June 2014 to July 2016. We have studied 110 asthenozoospermia and OAT infertile men whose semen profile indicated abnormal motility and 50 normal fertile controls. Of 110 infertile men, 70 had asthenozoospermia and 40 had OAT. Fractionations of spermatozoa were done in each semen sample on the basis of their motility by percoll gradients discontinuous technique. Long-range PCR was used for detection of 7436-bp deletions in sperm mtDNA and was confirmed by primer shift technique. RESULTS Overall eight subjects (8/110; 7.2%) of which six (6/70; 8.57%) asthenozoospermia and two (2/40; 5%) OAT had shown deletions of 7436-bp. In 40% percoll fraction had more non-motile spermatozoa than 80% percoll fraction. The non-motile spermatozoa in 40% percoll fractions showed more mtDNA deletions (7.2%) than the motile spermatozoa in 80% percoll fraction (2.7%). The sequencing of flanking regions of deleted mtDNA confirmed 7436-bp deletions. Interestingly, no deletions were found in control subjects. CONCLUSION Though, the frequency of 7436-bp deletions in sperm mtDNA was low in infertile cases but meaningful indications were there when results were compared with controls. It is indicated that large scale deletions 7436-bp of mtDNA is associated with abnormal sperm motility. The 7436-bp deletions of mtDNA in spermatozoa may be one of the important causes of dysfunction and non-motile sperm.

Communication between the musculocutaneous and median nerves in the arm.

interphalangeal joint (IPJ) extension of the thumb under traction of EPB reported recently can also add to the difficulty in identifying the EPB (Alemohammad et al., 2009). The 1,2 intercompartmental supraretinacular artery (ICSRA) travels between the first and second extensor compartments (Shin and Bishop, 2002). We prospectively investigated the usefulness and incidence of the 1,2 ICSRA as a surface marker in 33 patients having surgery to release this compartment. We identified the 1,2 ICSRA and regarded it as the ulnar margin of the first extensor compartment. After electrocauterization of the 1,2 ICSRA, longitudinal release of the first extensor compartment was carried out along the radial side of the 1,2 ICSRA. Then, we elevated the first extensor retinaculum as a radially based retinacular flap and completed the release. When we encountered a separate septum, it was easily identified within the first extensor compartment because it was located on the radial side of the EPB, and completely released. If we did not find the 1,2 ICSRA, we used the usual technique to find the EPB by observing passive extension of the MPJ of the thumb by applying traction. After confirming the complete release of the first extensor compartment, we left the elevated radial based retinacular flap in situ without repair. The 1,2 ICSRA was identified under 3.5 loupe magnification in 29 (87%) of the 33 patients. It had a straight course between the first and second extensor retinaculum and then a curved course at the distal margin of the extensor retinaculum (Fig 1). Its straight portion was always located longitudinally between the first and second extensor compartment and corresponded to the ulnar margin of the first extensor compartment. Its turning point corresponded to the distal margin of the first extensor retinaculum. A longitudinal incision along the side of the 1,2 ICSRA always opened the first extensor compartment at the most ulnar margin. A separate septum was found in 23 of the 33 patients (69%). The knowledge of the vascular networks of the dorsum of the wrist have been used only to raise a vascularized bone graft (Shin and Bishop, 2002) when treating Kienböck’s disease and scaphoid nonunion. The 1,2 ICSRA was present in 93% on the surface of the extensor retinaculum (Sheetz et al., 1995). The turning portion of the 1,2 ICSRA corresponded to the distal edge of the first extensor retinaculum. We feel that the use of the 1,2 ICSRA as a marker simplifies the operative procedure and will help reduce the number of failed operations caused by incomplete release of the EPB sheath.

Immunomodulatory potential of recombinant filarial protein, rWbL2, and its therapeutic implication in experimental ulcerative colitis in mouse

Abstract Objective: Immunomodulation by helminth proteins has potential therapeutic implications in inflammatory bowel disease. In the present study, we have explored the therapeutic effect of a RAL family protein of filarial parasite Wuchereria bancrofti i.e., rWbL2 protein against DSS induced colitis in a mouse model. Materials and methods: Anti-inflammatory activity of rWbL2 on mice peritoneal exudate cells was analyzed under in vitro condition. The colitis mice were treated intraperitoneally (i.p.) with rWbL2 in increasing doses (10 µg, 25 µg, and 50 µg) on days 4, 5, and 6. Disease severity was assessed by disease activity index (DAI), macroscopic and histopathological scores, and enzyme myeloperoxidase activity (MPO) in the colon. The response of the cultured splenocytes from treated mice to Con-A stimulation, in terms of ELISA-based assessment of the protein followed by the assessment of mRNA expression of cytokines, was measured by real-time PCR analysis. Result: rWbL2 protein showed anti-inflammatory activity in vitro. Treatment with rWbL2 (at 25 µg/dose) effectively attenuated disease severity by reducing weight loss, DAI, mucosal edema, colon damage, and MPO activity. This therapeutic effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of pro-inflammatory cytokine IFN-γ and TNF-α by the splenocytes of treated mice followed by stimulation with Con-A. Conclusions: These results provide evidence of the strong immunomodulatory potential of rWbL2 protein implicating its therapeutic application against ulcerative colitis.

Unilateral isolated incompletely duplicated ureter

The aim of this study was to report a congenital anomaly in a cadaveric dissection. During routine undergraduate dissection in a middle-aged male cadaver, we found that on the left side, there was a presence of an incompletely duplicated ureter. On the right side the ureter was single in its whole extent. No other congenital anomaly was found to be associated with this. The two limbs of the left ureter joined at about a distance of 5 cm from the bladder wall. A duplicated ureter is commonly found in association with other congenital anomalies and defects. The present case report describes a rare case of an isolated duplicated ureter with a normal kidney, urinary bladder, and renal vessels. This case report adds on to the literature and will be helpful and interesting for the surgeons. The possible embryological reasons for the formation of a duplicated ureter will be discussed.