The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS35 can regulate APP metabolism and Aβ formation, and its levels are reduced in Alzheimer’s disease (AD) brains. We and others demonstrated that VPS35 genetic manipulation modulates the phenotype of mouse models of AD. However, the translational value of this observation remains to be investigated. Triple transgenic mice were randomized to receive a pharmacological chaperone, which stabilizes the retromer complex, and the effect on their AD-like phenotype assessed. Compared with controls, treated mice had a significant improvement in learning and memory, an elevation of VPS35 levels, and improved synaptic integrity. Additionally, the same animals had a significant decrease in Aβ levels and deposition, reduced tau phosphorylation and less astrocytes activation. Our study demonstrates that the enhancement of retromer function by pharmacological chaperones is a potentially novel and viable therapy against AD.

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A pharmacological chaperone improves memory by reducing Aβ and tau neuropathology in a mouse model with plaques and tangles.

Objective To determine the prevalence of low sperm count including oligospermia and azoospermia in male infertile population, and to assess the pattern and distribution of abnormal semen parameters in infertile men. Methods The descriptive cross-sectional survey was carried out at the Department of Gynaecology and Obstetrics, Sharif Medical City Hospital, Lahore, from June 2009 to June 2010. A total of 500 consecutively consenting male partners of women fulfilling the inclusion criteria between 20 and 40 years of age were approached. Semen analysis was performed according to methods and standards defined by the World Health Organisation (WHO). Samples were categorised into normospermia, oligospermia and azoospermia on the basis of sperm count. After exclusion of azoospermic samples, normospermic and oligospermic samples were compared for ejaculated volume, pus cells, motility and morphology. SPSS 10 was used for statistical analysis. Results Out of the 500 males approached, 104 (20.8%) had to be left out either because of their unwillingness or inability to pass semen. The study sample comprised of 396 (response rate 79.2%); normospermia was observed in 293 (73.99%) males, azoospermia in 59 (14.89%), and oligospermia in 44 (11.11%). The oligospermic samples had low ejaculated volume, but significantly higher percentage of non-motile sperms 62% +/- 23.9% and abnormal morphology 55% +/- 15.6% in comparison to normospermic samples (p 0.0001). Asthenospermia was observed in 37 (25.81%), teratospermia in 11 (3.26%) and oligoasthenoteratospermia in 4 (9.09%) of samples. Conclusion Semen analysis is the cornerstone for the evaluation of infertility in men. Sperm concentration, motility and morphology are related to each other, factors that cause deterioration of one of them usually also have negative impact on the other two as well.

Semen analysis parameters: experiences and insight into male infertility at a tertiary care hospital in Punjab.

In order to provide an insight to the prevalence of low sperm count and abnormal semen parameters in suspected subfertile/infertile men in our environment, semen samples collected from one hundred and seventy (170) men aged 21-50 years, whose wives were seen at a private fertility clinic in Abakaliki, Nigeria with diagnosis of primary and secondary infertility (78 and 92 respectively) were analysed in accordance with World Health Organization guidelines. Significantly high proportion (70%) of the study population had low sperm count (p < 0.05) with significantly high defective parameters (64%). Asthenozoospermia and teratozoospermia were the major abnormal parameters recorded. Higher prevalence of oligospermia was found in the civil servants and age-group 31-40 years (74% and 75% respectively). Using 10(5) cfu/ml as a significant level of bacteria growth, the prevalence of bacteria growth was found to be 56% of which 18% were from normospermic semen d 38% from oligospermic semen.

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Prevalence of Low Sperm Count and Abnormal Semen Parameters in Male Partners of Women Consulting at Infertility Clinic in Abakaliki, Nigeria

Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats.

Evaluation of biochemical indices of male rat reproductive function and testicular histology in wistar rats following chronic administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Heirn) stem

Variations in semen analyses of 177 males over a 1 year period were assessed. The average means of total counts, motility, morphology, total motile count and non-motile % were determined for 5 classes of patients ranging from azoospermic to normospermic. Positive relationships between a falling sperm count, a decrease in motility and total motile counts were seen. Also, increasingly, abnormal forms were found with lower sperm counts.

Sperm motility and morphology as changing parameters linked to sperm count variations.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAVs) are characterized blood vessel inflammation and necrosis which may lead to diffuse alveolar hemorrhage (DAH) resulting in life threatening respiratory failure. We present a case of microscopic polyangiitis presented in respiratory failure secondary to DAH that developed a rare treatment related complication. A 50 year old lady presented in respiratory failure with hemoptysis & falling hemoglobin. Chest X-ray showed bilateral inhomogeneous opacities and urine showed granular casts and red blood cells. Red colored bronchoalveolar lavage was obtained and serology came positive for pANCA. She was treated with corticosteroid and rituximab. The patient improved initially, but later developed rituximab induced late onset neutropenia. She unfortunately developed pulmonary mucormycosis and could not be revived. Thus, rituximab behaved as a “double edge sword”, helping the patient initially but later making her susceptible for opportunistic infection.

Double edge sword

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Obstructive Sleep Apnea with Insomnia Overlap: An Under-recognized Entity

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Multiple Pulmonary Nodules in a Febrile Patient

Background: Restless leg syndrome (RLS) is common among patients with obstructive sleep apnoea (OSA) but the prognostic importance of this is not studied. We have called OSA and RLS coexistence as ComOSAR. Materials and Methods: A prospective observational study was done on patients referred for polysomnography (PSG) with the aims to evaluate 1) the prevalence of RLS in OSA and comparing it with RLS in non-OSA, 2) the prevalence of insomnia, psychiatric, metabolic and cognitive disorders in ComOSAR versus OSA alone, 3) chronic obstructive airway disease (COAD) in ComOSAR versus OSA alone. OSA, RLS and insomnia were diagnosed as per respective guidelines. They were evaluated for psychiatric disorders, metabolic disorders, cognitive disorders and COAD. Results: Of 326 patients enrolled, 249 were OSA and 77 were non-OSA. 61/249 OSA patients, i.e. 24.4% had comorbid RLS, i.e. ComOSAR. RLS in non-OSA patients was similar (22/77, i.e. 28.5%); P = 0.41. ComOSAR had a significantly higher prevalence of insomnia (26% versus 10.1%; P = 0.016), psychiatric disorders (73.7% versus 48.4%; P = 0.00026) and cognitive deficits (72.1% versus 54.7%, P = 0.016) compared to OSA alone. Metabolic disorders like metabolic syndrome, diabetes mellitus, hypertension and coronary artery disease were also observed in a significantly higher number of patients with ComOSAR versus OSA alone (57% versus 34%; P = 0.0015). COAD was also seen in a significantly higher number of patients with ComOSAR compared to OSA alone (49% versus 19% respectively; P = 0.00001). Conclusion: It is essential to look for RLS in patients with OSA as it leads to a significantly higher prevalence of insomnia, and cognitive, metabolic and psychiatric disorders. COAD is also more common in ComOSAR compared to OSA alone.

SR Vaidya

Papers

Sperm motility and morphology as changing parameters linked to sperm count variations.

Double edge sword

Obstructive Sleep Apnea with Insomnia Overlap: An Under-recognized Entity

Multiple Pulmonary Nodules in a Febrile Patient

A study on the prevalence of RLS in OSA and the consequences of co-occurrence