Minireview: mechanisms by which the metabolic syndrome and diabetes impair memory

Type 2 diabetes is associated with an increased risk of cognitive dysfunction. These effects seem particularly true for memory functions. This article examines how diabetes and the biological changes that occur with diabetes such as hyperglycemia, changes in insulin concentration, hypertension, and changes in lipid levels might lead to these alterations in cognitive functioning, with an emphasis on the mechanisms leading to changes in memory.     

Hypertriglyceridemia: a possible diagnostic marker of disease severity in visceral leishmaniasis

Purpose

Visceral leishmaniasis (VL), a protozoan disease, is 100 % fatal if left untreated. Anemia is common in VL which plays a role in expression of clinically overt VL disease. Laboratory clues are scarce for strengthening clinical suspicion for severity in VL. Hypertriglyceridemia has emerged as a new concept for the diagnosis and prognosis in VL. The present study is aimed at correlating the magnitude of hypertriglyceridemia with the severity in VL.

Materials and methods

A retrospective case–control study was conducted between January 2012 to December 2013 among 124 patients coming for treatment from VL endemic areas, who had fever of more than 15 days and did not respond to antimalarials and antibiotics. The parasitologically confirmed VL cases (n = 87) were categorized as mild/moderate (n = 60) and severe (n = 27) groups according to WHO classification for anemia and parasite burden. Serum triglycerides were assayed in VL groups along with controls (n = 37).

Results

Serum triglyceride level was significantly higher in VL than controls [mean values were 173.50 ± 47.67 versus 127.1 ± 53.79 mg/dl, respectively (p < 0.0001)]. Triglyceride level was significantly higher in severe than in mild/moderate group of VL [211.3 ± 50.2 mg/dl versus 134 ± 45.09 mg/dl, respectively (p < 0.0001)]. Hypertriglyceridemia (>161.7 mg/dl) was noted in all severe VL patients, compared to 31.66 % of mild or moderate group (p < 0.0001). There was no significant difference between mild/moderate VL and controls.

Conclusions

It is hypothesized that hypertriglyceridemia could be of additional diagnostic benefit to assess the probability and severity of VL in endemic areas.

     

Pheochromocytoma: a 10-year experience in a tertiary care North Indian hospital.

BACKGROUND: The study was carried out to highlight the clinical and biochemical profile of patients with pheochromocytoma in a tertiary care center of North India. METHODS AND RESULTS: Thirty consecutive cases of pheochromocytoma admitted over a period of 10 years to our Institute were analyzed. The chief clinical complaints of these 30 patients (17 males and 13 females, mean age 24+/-7 years) were palpitation (80%), headache (77%), sweating (60%), breathlessness (67%) and flushing (56%). The clinical triad of headache, flushing and sweating occurred in 26.7% of cases. On clinical examination, 97% of the patients were hypertensive and 16.6% presented with malignant hypertension. Laboratory measurements showed that the levels of 24-hour urinary vanillylmandelic acid were elevated in 80% of cases. Levels of plasma adrenaline and noradrenaline were raised in 78% and 79% of cases, respectively. Anatomical localization of the tumor on computerized tomographic scan showed the presence of an adrenal tumor in 80% and extra-adrenal tumor in 20%. Surgical removal of the tumor could be carried out in 28 cases following control of the blood pressure with antihypertensive drugs including alpha and beta adrenoreceptor blockers. CONCLUSIONS: Pheochromocytoma should be suspected in all young hypertensive persons. The appropriate therapy for this tumor is surgical removal preceded by adequate blood pressure control including the use of alpha and beta adrenoreceptor antagonists.     

Putative roles of a proline–glutamic acid-rich protein (PE3) in intracellular survival and as a candidate for subunit vaccine against Mycobacterium tuberculosis

The proline–glutamic acid (PE) protein family of Mycobacterium tuberculosis (Mtb) plays diverse roles in the pathogenesis and modulation of host immune responses. The uniqueness of conserved regions of PE proteins may be useful to test and validate their corresponding functions. Hence, the present study has been undertaken to demonstrate the role of PE3 (Rv0159c) for persistence, host immune response and immunoprophylaxis. We have expressed Mtb-specific PE3 gene in M. smegmatis (MS) and used the strain to infect J774A.1 macrophage cells and BALB/c mice. It was observed that during the infection, the MS expressing PE3 showed higher bacterial load when compared to infection with wild-type MS. In hypoxic condition, the expression level of PE3 gene was induced in Mtb, which further showed its relevance in the cell survival during hypoxia-induced persistence. The expression level of PE3 in Mtb was markedly induced during chronic stage of murine infection, which reiterated its importance in mycobacterial persistence in the host. The immunization of mice with recombinant PE3 protein stimulated the secretion of TNF, IL-6 and IL-2 cytokines and generated strong protective immunity against challenge with live mycobacteria, which was evidenced by decreased viable bacilli in the lungs, histopathological changes and increased survival of PE3 immunized mice. Conclusively, the results indicated that PE3 plays significant roles in mycobacterial persistence during infection, modulate host immune response and hence could be a prospective candidate for the development of subunit vaccine against tuberculosis.     

Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.     

Anterior segmental osteotomies without orthodontics: practicability of the correction of dentoalveolar deformities

We designed this study to determine the efficiency and stability of anterior segmental osteotomies (ASO) without orthodontics for various dentofacial deformities. Records of patients treated with maxillary or mandibular ASO, or both, without orthodontics in the past 15 years were analysed. The assessment included postoperative analysis of patients’ aesthetics and functional satisfaction using a questionnaire and grading (score 0 - 4) system, and the amount of relapse calculated from 12-month postoperative cephalograms. A total of 26 ASO subjects (age range 13- 31 years) were studied (14 maxillary, two mandibular, and 10 bimaxillary). Long-term stability was acceptable in all cases with no significant relapse (p>0.05). No major complications were encountered. All patients reported good to excellent (score = 3 to 4) satisfaction following surgery. Using meticulous planning and a careful surgical technique, ASO without orthodontics is a simple, quick, safe, and stable option for the correction of dentofacial deformities.     

Diagnosis of tuberculous meningitis: clinical and laboratory parameters.

BACKGROUND: Confirming the clinical suspicion of tuberculous meningitis (TBM) has always been problematic. Whilst smear and culture positivity are diagnostic, these tests have low sensitivity. The polymerase chain reaction (PCR) assay has given variable results. AIM: This study attempted to improve the diagnostic yield by: (a) increasing the cerebrospinal fluid (CSF) volumes; (b) testing the yield from three specimens of CSF assumed to represent lumbar, cervico-thoracic cord, and base of brain CSF samples; (c) undertaking PCR assays using multiple primer sets; and (d) using real-time PCR. METHOD: Patients suspected of having cranial or spinal meningeal tuberculosis were entered into the study. Three aliquots of CSF were subjected to smear, culture, and conventional and real-time PCR. Three sets of primers - IS6110, MPB64, and PT8/9 - were used. Patients were retrospectively classified into four categories: 'definite TB' (culture positive), 'probable TB' (clinical and other tests suggestive of TB), 'not TB', and 'uncertain diagnosis'. RESULTS: A total of 68 patients were studied. There were 20 patients classified as definite TB, 24 probable TB, 17 not TB, and seven uncertain diagnosis. Forty-eight of 57 (84.2%) patients tested were HIV seropositive. The IS6110 PCR was positive in 27 patients which included 18/20 culture positive cases, six in the probable TB group, and three in the not TB group. The MPB64 and PT8/9 primers did not increase the yield. Real-time PCR was positive in seven additional patients. Combining the definite and probable TB, the sensitivity of all PCR assays was 70.5% (31/44) and specificity 87.5% (21/24). CONCLUSION: Targeting multiple sites of the TB genome using conventional PCR did not increase the number of positive cases. Real-time PCR was more sensitive. However, all the current techniques are still too insensitive to confidently exclude the diagnosis on laboratory grounds.