Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Penile malignant peripheral nerve sheath tumour (schwannoma) in a three-year-old child without evidence of neurofibromatosis.

Malignant schwannoma (malignant peripheral nerve sheath tumour, MPNST) is a rare high-grade tumour arising from peripheral nerves. We report the case of a 3-year-old male who presented with a non-tender lesion on the dorsum of his penis. The lesion was excised and a formal circumcision performed. Histology of the lesion revealed a spindle cell tumour. Immunohistochemistry showed the tumour cells to be strongly positive for S100 and Vimentin. A diagnosis of intermediate grade malignant peripheral nerve sheath tumour was made. Malignant schwannoma is rare in children and is previously unreported in the penis in the paediatric age group without evidence of neurofibromatosis.     

Resistance of Drosophila to cadmium: biochemical factors in resistant and sensitive strains

With regard to cadmium toxicity, Drosophila strains v;bw and Austin represent extremes in resistance and sensitivity, respectively. Both strains produced metallothionein (MT) in response to Cd ions in their diet. Austin produced more metallothionein than v;bw at Cd ion levels below 0.2 mM, when both strains were allowed lifetime development on Cd2+-containing media. When the rate of MT appearance was measured for 4 days in young adults the results showed no clear trend with time within a strain or between strains. The plot of LC50 vs. MT levels for identical developmental conditions revealed that for v;bw small increases in MT corresponded to large increases in resistance whereas for the sensitive Austin even large increases in MT had comparatively little effect on increasing LC50. Results given here suggest that differences in total MT content do not explain the genetically demonstrable difference in Cd2+-resistance between v;bw and Austin. However, since two MT genes are identified in Drosophila, differences in resistance could be reflective of greater relative amounts of one "more important" MT in the resistant fly.     

Subchronic exposure to arsenic through drinking water alters expression of cancer-related genes in rat liver

Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in drinking water), by using real-time quantitative RT-PCR and immunohistochemical analyses. Arsenic accumulated in the rat liver dose-dependently and caused hepatic histopathological changes, such as disruption of hepatic cords, sinusoidal dilation, and fatty infiltration. A 1-month exposure to arsenic significantly increased hepatic mRNA levels of cyclin D1 (10 ppm), ILK (1 ppm), and p27(Kip1) (10 ppm), whereas it reduced mRNA levels of PTEN (1 ppm) and beta-catenin (100 ppm). In contrast, a 4-month arsenic exposure showed increased mRNA expression of cyclin D1 (100 ppm), ILK (1 ppm), and p27(Kip1) (1 and 10 ppm), and decreased expression of both PTEN and beta-catenin at all 3 doses. An immunohistochemical study revealed that each protein expression accords closely with each gene expression of mRNA level. In conclusion, subchronic exposure to inorganic arsenate caused pathological changes and altered expression of cyclin D1, p27(Kip1), ILK, PTEN, and beta-catenin in the liver. This implies that arsenic liver toxicity involves disturbances of some cancer-related molecules.     

Sperm binding to hyaluronan is an excellent predictor of Nili-Ravi buffalo bull fertility

This study reports the first evaluation of sperm hyaluronan binding assay (HBA) for predicting the fertility of Nili-Ravi buffalo bulls in relation to standard parameters of sperm quality. Cryopreserved semen doses of low (n = 6), medium (n = 3) and high fertility (n = 8) bulls based on their respective return rates were used. Significantly, more spermatozoa bound to hyaluronan from the most fertile bulls (57.15% ± 1.44) compared with medium (42.46% ± 1.08) and low fertility bulls (29.70% ± 0.78). A strongly positive correlation (r = .824, p < .01) was found between HBA and fertility that predicts a 67.9% variability (r² = .679, p < .01) in fertility. HBA was also strongly positively correlated with sperm viability (r = .679, p < .01) followed by their live/dead ratio (r = .637, p < .01), uncapacitated spermatozoa (r = .631, p < .01), normal apical ridge (r = .459, p < .01), motility (r = .434, p < .01), mature spermatozoa with low residual histones (r = .364, p < .01), high plasma membrane integrity (r = .316, p < .01) and nonfragmented DNA levels (r = .236, p < .05). It was negatively correlated with spermatozoa having reacted acrosome (r = −.654, p < .01). A fertility model built using a combination of sperm HBA and either sperm livability or viability predicts, respectively, 86.1% (r² = .861, p < .01) and 85.9% (r² = .859, p < .01) variability in buffalo bull fertility. In conclusion, sperm HBA may prove to be a single robust predictor of Nili-Ravi buffalo bull fertility.     

Effectiveness of the caverno-dorsal vein shunt (Barry shunt) on prolonged ischaemic priapism and its effect on the post-operative long-term erectile function

Ischaemic priapism is the most common form of priapism and requires urgent treatment. In this study, we evaluated the effectiveness of the caverno-dorsal vein shunt on resolution of ischaemic priapism and on the post-operative long-term erectile function in patients presenting with priapism. The study included 10 patients admitted to our hospital for priapism between 2010 and 2018. The median age of the patients was 31 (24–66) years. The median priapism time was 13.5 (7–38) hours. The blood gas measurements were taken from the corpus cavernosum, and the drainage of the corpus cavernosum was performed as an emergency intervention. Then, the corpus cavernosum was irrigated with 0.01% adrenaline 5 times in 20-min intervals. The caverno-dorsal vein shunt procedure was performed in cases without regression of priapism. Two months after, the operation shunt was closed. Detumescence occurred in all patients. Eight of 10 patients maintained their erectile function. In 2 patients, severe erectile dysfunction occurred at post-operative 2 months following a priapism attack and penile prosthesis implantation was performed in these 2 patients. Our study showed that caverno-dorsal vein shunt procedure is effective in providing detumescence and maintaining potency in cases with ischaemic priapism. In our opinion, caverno-dorsal vein shunt can be considered as the first treatment of choice for refractory low-flow priapism.