Annular pancreas in an adult managed by laparobotic surgery: a case report

Annular pancreas in an adult is an uncommon and infrequently reported anomaly which is characterized by the presence of ectopic pancreatic tissue surrounding the descending part of the duodenum. It is one of the few congenital anomalies of the gastrointestinal tract, which can manifest with symptoms late in life (Ravitch and Woods in Ann Surg 132:1116–1127, 1950). In adults, the factors initiating symptoms are recurrent pancreatitis, duodenal stenosis at the site of the annulus, or duodenal or gastric ulceration (Morrell and Keynes in Br J Surg 57:814–816, 1970). Operative management of these cases involves bypassing the obstructed duodenum. Duodenoduodenostomy is routinely performed in neonates and children. We report a case of annular pancreas in a 55-year-old male that was successfully treated with robotic duodenoduodenostomy.     

An interpretative phenomenological analysis (IPA) of coercion towards community dwelling older adults with dementia: findings from Mysore studies of natal effects on ageing and health (MYNAH)

Purpose

Limited availability of specialist services places a considerable burden on caregivers of Persons with Dementia (PwD) in Low- and Middle-Income Countries (LMICs). There are limited qualitative data on coercive behavior towards PwD in an LMIC setting.

Aim

The aim of this study was to find relevant themes of the lived experience of relatives as caregivers for PwD in view of their use of coercive measures in community setting in South India.

Method

Primary caregivers (n = 13) of PwDs from the Mysore study of Natal effects on Ageing and Health (MYNAH) in South India were interviewed to explore the nature and impact of coercion towards community dwelling older adults with dementia. The narrative data were coded using an Interpretative Phenomenological Analysis (IPA) approach for thematic analysis and theory formation.

Results

Caregivers reported feeling physical and emotional burn-out, a lack of respite care, an absence of shared caregiving arrangements, limited knowledge of dementia, and a complete lack of community support services. They reported restrictions on their lives through not being able take employment, a poor social life, reduced income and job opportunities, and restricted movement that impacted on their physical and emotional well-being. Inappropriate use of sedatives, seclusion and environmental restraint, and restricted dietary intake, access to finances and participation in social events, was commonly reported methods of coercion used by caregivers towards PwD. Reasons given by caregivers for employing these coercive measures included safeguarding of the PwD and for the management of behavioral problems and physical health.

Conclusion

There is an urgent need for training health and social care professionals to better understand the use of coercive measures and their impact on persons with dementia in India. It is feasible to conduct qualitative research using IPA in South India.

     

Differential toxicity profile of ricin isoforms correlates with their glycosylation levels

Ricin is one of the most potent and deadly plant toxins from the seeds of Ricinus communis. In view of its high toxicity, ricin is being used as an immunotoxin in cancer therapy. Ricin also has several isoforms with differential glycosylation depending on the seed variety. Our study shows three isoforms designated 1, 2 and 3, which differed in their surface charge, resulting in a different behavior on cation exchange chromatography, two dimensional (pI 5.5-8.7) and native PAGE. The molecular masses of isoform-1, 2 and 3 were measured as 63.55 kDa, 64.03 kDa and 62.8 kDa, respectively, by MALDI-TOF/MS. In vitro studies with monkey kidney (Vero) cells showed a time dependent increase in cytotoxicity of the isoforms evaluated by extracellular lactate dehydrogenase activity and mitochondrial dehydrogenase assay. These isoforms also induce oxidative stress and DNA damage. Among the isoforms, isoform-3 was quick to generate reactive oxygen species (ROS), (in 90 min) and exhibited maximum cytotoxicity. Morphological changes, catalase activity and DNA fragmentation were significantly higher with isoform-3 treatment compared to others. The glycosylation studies by MALDI-TOF/MS showed that isoform-3 is highly glycosylated with high sugar levels containing more of hybrid/complex type glycopeptides with mannose as hexose units. These experimental evidences clearly suggest that isoform-3 is superior in its early ROS generation, potency to induce oxidative stress and cytotoxicity, that could be due to it's higher glycosylation levels which make isoform-3 as an ideal candidate for immunotoxin studies.     

Impaired spatial and non-spatial configural learning in patients with hippocampal pathology

The hippocampus has been proposed to play a critical role in memory through its unique ability to bind together the disparate elements of an experience. This hypothesis has been widely examined in rodents using a class of tasks known as "configural" or "non-linear", where outcomes are determined by specific combinations of elements, rather than any single element alone. On the basis of equivocal evidence that hippocampal lesions impair performance on non-spatial configural tasks, it has been proposed that the hippocampus may only be critical for spatial configural learning. Surprisingly few studies in humans have examined the role of the hippocampus in solving configural problems. In particular, no previous study has directly assessed the human hippocampal contribution to non-spatial and spatial configural learning, the focus of the current study. Our results show that patients with primary damage to the hippocampus bilaterally were similarly impaired at configural learning within both spatial and non-spatial domains. Our data also provide evidence that residual configural learning can occur in the presence of significant hippocampal dysfunction. Moreover, evidence obtained from a post-experimental debriefing session suggested that patients acquired declarative knowledge of the underlying task contingencies that corresponded to the best-fit strategy identified by our strategy analysis. In summary, our findings support the notion that the hippocampus plays an important role in both spatial and non-spatial configural learning, and provide insights into the role of the medial temporal lobe (MTL) more generally in incremental reinforcement-driven learning.     

Senescence mediated redox imbalance in cardiac tissue: Antioxidant rejuvenating potential of green tea extract

ObjectiveThe activities and capacities of antioxidant systems of tissue cells are declined during aging, leading to the gradual loss of pro-oxidant/antioxidant balance and accumulation of oxidative damage. Hence, the present study evaluated the role of green tea extract (GTE), rich in polyphenols, in combating age-associated macromolecular damage in rat cardiac tissue.MethodsThe antioxidant defense system, lipid peroxidation, protein oxidation, and redox status in heart tissue were studied using young and aged rats.ResultsSignificant increases in lipid peroxidation, protein carbonyls, and marked decreases in glutathione redox status, protein thiols, and activities of enzymatic and non-enzymatic antioxidants were observed in aged rats compared with young rats. Supplementation of GTE (100 mg/kg of body weight per day) orally for 30 days ameliorated these changes significantly.ConclusionThis study accredits GTE's antioxidant rejuvenating potency and its role in the amelioration of senescence-mediated redox imbalance in aged rat cardiac tissue.     

O-fucosylation of muscle agrin determines its ability to cluster acetylcholine receptors

Protein O-fucosyltransferase 1 (Pofut1) transfers fucose to serine or threonine on proteins, including Notch receptors, that contain EGF repeats with a particular consensus sequence. Here we demonstrate that agrin is O-fucosylated in a Pofut1-dependent manner, and that this glycosylation can regulate agrin function. Fucosylation of recombinant C45 agrin, both active (neural, z8) and inactive (muscle, z0) splice forms, was eliminated when agrin was overexpressed in Pofut1-deficient cells or by mutation of a consensus site for Pofut1 fucosylation (serine 1726 in the EGF4 domain). Loss of O-fucosylation caused a gain of function for muscle agrin such that it stimulated AChR clustering and MuSK phosphorylation in cultured myotubes at levels normally only found with the neural splice form. Deletion of Pofut1 in cultured primary myotubes and in adult skeletal muscle increased AChR aggregation. In addition, Pofut1 gene and protein expression and Pofut1 activity of the EGF4 domain of agrin were modulated during neuromuscular development. These data are consistent with a role for Pofut1 in AChR aggregation during synaptogenesis via the regulation of the synaptogenic activity of muscle agrin.     

Kinetics of glyburide metabolism by hepatic and placental microsomes of human and baboon

Glyburide (glibenclamide) is under investigation for treatment of gestational diabetes. Two metabolites of glyburide have been previously identified in patients, namely, 4-trans-(M1) and 3-cis-(M2) hydroxycyclohexyl glyburide. Recently, the metabolism of glyburide by microsomes of liver and placenta from humans and baboons revealed the formation of four additional metabolites: 4-cis-(M2a), 3-trans-(M3), and 2-trans-(M4) hydroxycyclohexyl glyburide, and ethyl-hydroxy glyburide (M5). The aim of this investigation was to determine the kinetics for the metabolism of glyburide by cytochrome P450 (CYP) isozymes of human and baboon placental and hepatic microsomes. The metabolism of glyburide by microsomes from the four organs revealed saturation kinetics and apparent K(m) values between 4 and 12 microM. However, the rates for formation of the metabolites varied between organs and species. M1 was the major metabolite (36% of total), formed by human hepatic microsomes with V(max) of 80+/-13 pmol mg protein(-1)min(-1), and together with M2, accounted for only 51% of the total. M5 was the major metabolite (87%) formed by human placental microsomes with V(max) of 11 pmol mg protein(-1)min(-1). In baboon liver, M5 had the highest rate of formation (V(max) 135+/-32 pmol mg protein(-1)min(-1), 39% of total), and in its placenta, was M4 (V(max) 0.7+/-0.1 pmol mg protein(-1)min(-1), 65%). The activity of human and baboon hepatic microsomes in metabolizing glyburide was similar, but the activity of human and baboon placental microsomes was 7% and 0.3% of their respective hepatic microsomes. The data obtained suggest that more than 1 CYP isozyme is responsible for catalyzing the hydroxylation of glyburide.