Oxidative injury by peroxynitrite in neural and vascular tissue of the lateral geniculate nucleus in experimental glaucoma

In glaucoma, recent studies show that neural degeneration extends beyond the retinal ganglion cells to include target neurons in the lateral geniculate nucleus of the brain. The pathobiology of LGN degeneration in glaucoma is as yet unknown. We investigated whether peroxynitrite-mediated oxidative stress plays a role in glaucomatous degeneration of the LGN. Nitrotyrosine (NT), a marker for peroxynitrite-mediated oxidative injury, was studied in right LGN sections from monkeys with experimental unilateral glaucoma in the right eye and from normal controls. Immunoreactivity for NT was analyzed using bright-field microscopy. The density of NT profiles localized in neural tissue was determined for LGN layers (2,3,5) connected to the glaucoma eye and LGN layers (1,4,6) connected to the non-glaucoma eye. Density was calculated for each LGN layer by dividing the number of NT profiles by the cross-sectional area of each LGN layer. Blood vessels in each LGN were examined for NT formation. NT formation was detected in LGN layers of all monkeys with glaucoma. Quantitative analysis revealed that compared to controls, the density of NT profiles was increased in monkeys with glaucoma in LGN layers connected to glaucoma and non-glaucoma eyes. The mean density of NT profiles (+/-SEM) in neural tissue was significantly increased in glaucoma LGN layers compared to those of controls (2.30+/-0.56 vs. 0.29+/-0.12; P=0.016). Nitrotyrosine was readily apparent in LGN blood vessel endothelium in glaucoma, and not detected in blood vessels of control LGNs. The presence of NT in neural and vascular tissue of the glaucomatous LGN implicates peroxynitrite-mediated oxidative cell injury in the pathobiology of central neural degeneration in glaucoma.     

Longitudinal growth of head circumference in term symmetric and asymmetric small for gestational age infants

Aims

To study longitudinal growth pattern of head circumference of full-term symmetric and asymmetric small for gestational age (SGA) infants of the two sexes during first year of life.

Study Design

Mixed-longitudinal growth research design.

Subjects

Head circumference amongst full-term 100 symmetric, 100 asymmetric as well as 100 appropriate for gestational age (AGA) infants was measured at birth, 1, 3, 6, 9 and 12 months of age using standardized technique and instrument.

Results

The mean head circumference of male symmetric SGA infants measured significantly (p ≤ 0.001) smaller than asymmetric SGA infants while, in female symmetric SGA infants it measured shorter beyond 6 months. As compared to AGA infants, head circumference in symmetric and asymmetric SGA infants measured significantly smaller in size. Growth velocity for head circumference amongst symmetric and asymmetric SGA male infants did not show statistically significant differences. Rate of head circumference growth remained significantly higher amongst female asymmetric SGA infants than the symmetric ones between 3 and 6 months while, a reversal of trend was observed between 9 and 12 months.

Conclusion

The better growth attainments for head circumference of male and female asymmetric SGA infants than their symmetric SGA counterparts during first postnatal year of life may be attributed to the continuation of influence of “head sparing” experienced by asymmetric SGA babies during prenatal life.     

Enhanced influenza virus-like particle vaccines containing the extracellular domain of matrix protein 2 and a Toll-like receptor ligand

The extracellular domain of matrix protein 2 (M2e) is conserved among influenza A viruses. The goal of this project is to develop enhanced influenza vaccines with broad protective efficacy using the M2e antigen. We designed a membrane-anchored fusion protein by replacing the hyperimmunogenic region of Salmonella enterica serovar Typhimurium flagellin (FliC) with four repeats of M2e (4.M2e-tFliC) and fusing it to a membrane anchor from influenza virus hemagglutinin (HA). The fusion protein was incorporated into influenza virus M1-based virus-like particles (VLPs). These VLPs retained Toll-like receptor 5 (TLR5) agonist activity comparable to that of soluble FliC. Mice immunized with the VLPs by either intramuscular or intranasal immunization showed high levels of systemic M2-specific antibody responses compared to the responses to soluble 4.M2e protein. High mucosal antibody titers were also induced in intranasally immunized mice. All intranasally immunized mice survived lethal challenges with live virus, while intramuscularly immunized mice showed only partial protection, revealing better protection by the intranasal route. These results indicate that a combination of M2e antigens and TLR ligand adjuvants in VLPs has potential for development of a broadly protective influenza A virus vaccine.     

Cutaneous Microangiopathic Thrombosis Complicated by Pyoderma Gangrenosum in Post-Cardiac Surgery Heparin-Induced Thrombocytopaenia

Thrombotic cutaneous gangrene is a rare complication of heparin-induced thrombocytopaenia after cardiac surgery. We report a case and discuss management issues with cardiopulmonary bypass for cardiac surgery in this condition.     

Simple anthropometric measures identify fasting hyperinsulinemia and clustering of cardiovascular risk factors in Asian Indian adolescents

Correlations of easily measurable parameters of obesity (body mass index [BMI], waist circumference [WC], and subscapular skinfold thickness) with fasting hyperinsulinemia and cardiovascular risk factors (CRFs) have not been investigated in adolescents. We evaluated the screening performance of 3 anthropometric measurements, BMI, WC, and subscapular skinfold thickness, in identifying fasting hyperinsulinemia and clustering of CRFs in 680 male and 521 female adolescents and young adults aged 14 to 18 years in a cross-sectional population survey. CRFs considered were hypercholesterolemia, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, impaired fasting blood glucose, hypertension, and fasting hyperinsulinemia. The ability of the anthropometric measurements to identify the clustering of CRFs without (cluster 1) and with fasting hyperinsulinemia (cluster 2), and fasting hyperinsulinemia alone was evaluated. BMI, WC, and subscapular skinfold thickness identified the clustering of CRFs and fasting hyperinsulinemia better in males than in females. Among individual risk factors, WC was better in identifying the presence of 3 or more risk factors in cluster 1 for both males and females, and in cluster 2 in females. Subscapular skinfold thickness was better than BMI and WC in identifying hyperinsulinemia in males, and the presence of 3 or more risk factors in cluster 2 in females. All 3 measurements were more accurate in identifying fasting hyperinsulinemia than presence of 3 or more CRFs in either cluster 1 or cluster 2 with higher odds ratio for males. This study shows gender differences in identification of insulin resistance and clustering of CRFs by using simple anthropometric parameters in Asian Indian adolescents. These simple measurements are useful for preventing and predicting cardiovascular risk and for generating a correct definition of the metabolic syndrome.     

Schwannomas of Head and Neck and Review of Literature

Benign nerve cell tumours have been given various names like schwannoma, neurilemmoma, neurinoma, neurofibroma, spindle cell tumours etc. Extra cranial head and neck schwannomas usually present as solitary and well-demarcated lesions. The lesion can cause secondary symptoms, such as nasal obstruction, dysphasia, and hoarseness, depending upon the location of the lesion. Fine needle aspiration cytology, CT scans, and MRI may be of limited help in the diagnosis of schwannomas. The treatment is complete surgical excision of the benign tumour and postoperative histopathological examination establishes the final diagnosis.     

Environmental enrichment-mediated functional improvement after experimental traumatic brain injury is contingent on task-specific neurobehavioral experience

Environmental enrichment (EE) is superior to standard (STD) housing in promoting functional recovery after traumatic brain injury (TBI). However, whether the EE-mediated benefits after TBI are dependent on exposure to enrichment during neurobehavioral training has not been elucidated. To address this issue, isoflurane-anesthetized adult male rats received either a cortical impact or sham injury and were then randomly assigned to early EE, delayed EE, continuous EE or no EE (i.e., STD conditions). Continuous EE or no EE was initiated immediately after surgery and continued for the duration of the study. Early EE began directly after surgery, continued for 1 week, and was then followed by STD living (2 rats per cage) for the remainder of the study, while delayed EE commenced 1 week after early STD housing. Functional outcome was assessed with established motor and cognitive tests on post-injury days 1-5 and 14-18, respectively. CA(1)/CA(3) neurons were quantified at 3 weeks. CA(3) cell loss was significantly attenuated in the TBI+continuous EE group versus the TBI+no EE group. Beam-walking was facilitated in the TBI groups that received either early or continuous EE versus those receiving delayed or no EE. Cognitive training was enhanced in the TBI groups that received continuous or delayed EE versus the early EE or no EE groups. These data suggest that EE-mediated functional improvement after TBI is contingent on task-specific neurobehavioral experience.