Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1

Indian Journal of Pediatrics - Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder, characterized by dysregulated insulin secretion. Pathogenic variants in at...     

Concomitant parasitism: bancroftian filariasis and intestinal helminths and response to albendazole

Subjects in an disease-endemic area in Orissa, India concomitantly infected with filariasis and intestinal helminths had significantly lower intensity of filarial infection in comparison with those who were infected only with filariasis. Administration of albendazole resulted in a significant decrease in the prevalence of filarial antigenemia in subjects concomitantly infected with intestinal helminths, but produced little change in this infection measure in subjects infected only with Wuchereria bancrofti. These results indicate that intestinal helminths could play a role in the anti-filarial activity of albendazole, most probably by depressing filarial infection intensity in co-infected individuals. Confirmation of these findings in a larger cohort may yield important new insights regarding the role of using albendazole in the ongoing intervention programs for the control of lymphatic filariasis.     

High Tregs and systemic IL-10 expressions linked to the absence of sheath antibodies in lymphatic filariasis: implications on the persistence of residual infection

The persistence of residual infection is one of the major factors in failure of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). The present study aims to explore the status of sheath antibody and regulatory T cells (Tregs) known to play key roles in clearance of parasite and patent filarial infection, in individuals with residual infection after MDA. A total of 61 microfilaremic (Mf) individuals were followed up after at least 6 rounds of MDA. Infection status of subjects was assessed through the detection of Mf and circulating filarial antigen (CFA). Antibodies to Mf sheath were determined by immuno-peroxidase assay (IPA). The expression of Tregs was measured by a flow cytometer. IL-10 and IFN-γ were evaluated using the commercially available ELISA kit. The sheath antibody was present in subjects who have cleared both Mf and CFA and absent in individuals who were found to be Mf /CFA positive. Further individuals carrying infection have significantly high levels of Tregs and IL-10. A positive correlation was observed between Tregs, IL-10, and CFA in infected individuals. In contrast, a negative correlation was observed between IFN-γ and IL-10 in both infected and uninfected subjects. Our study reveals that the absence of a sheath antibody and a high level of Tregs and IL-10 are the hallmarks of the persistence of residual filarial infection.

     

Antibodies to diethylcarbamazine cross-react with microfilariae of Wuchereria bancrofti

Antibodies directed against the microfilarial sheath have been instrumental in the immune elimination of circulating microfilariae in human lymphatic filariasis. We report here that antibodies to diethylcarbamazine (DEC, the most commonly used anti-filarial drug) cross-react with the sheath of Wuchereria bancrofti microfilariae. Antibodies with reactivity to DEC were raised in rabbits by immunization with a conjugate of methylpiperazine carboxylic acid (MPCA, an acid hydrolysis product of DEC) coupled to bovine serum albumin. The reactivity of these antibodies with microfilarial sheath of W. bancrofti was demonstrated by indirect immunofluorescent assay and indirect immunoperoxidase assay. This reactivity could be effectively inhibited by pre-incubation of the antisera with different haptens such as DEC, MPCA or piperazine citrate.     

Temporal evolution of viscoelasticity of soft colloid laden air–water interface: a multiple mode microrheology study

Mechanical properties of particle laden interfaces is crucial for various applications. For water droplets containing soft microgel particles, passive microrheology studies have revealed that the dynamically varying surface area of the evaporating drop results in a viscous to viscoelastic transition along the plane of the interface. However, the behaviour of the medium orthogonal to the interface has been elusive to study using passive microrheology techniques. In this work, we employ optical tweezers and birefringent probe particles to extract the direction-resolved viscoelastic properties of the particle–laden interface. By using special types of birefringent tracer particles, we detect not only the in-plane translational mode but also the out-of-plane translational (perpendicular to the interface) and rotational modes. We first compare different passive methods of probing the viscoelasticity of the microgel laden interface of sessile drop and then study the modes perpendicular to the interface and the out-of-plane rotational mode using optical tweezers based passive microrheology. The viscoelasticity of the interface using two different methods, i.e., multiple-particle tracking passive microrheology using video microscopy and by trapping birefringent tracer particles in optical tweezers, relying on different models are studied and found to exhibit comparable trends. Interestingly, the mode orthogonal to the interface and the rotational mode also show the viscous to viscoelastic transition as the droplet evaporates, but with lesser viscoelasticity during the same evaporation time than the in-plane mode.

Mechanical properties of particle laden interfaces is crucial for various applications.     

Antibodies to microfilarial sheath in bancroftian filariasis--prevalence and characterization

Antibodies directed towards the sheaths of microfilariae have been implicated in the elimination of circulating microfilariae, both in experimental and human filariasis. In the present study antisheath antibodies have been detected in human sera by indirect immunoperoxidase assay (IPA) using fixed Wuchereria bancrofti microfilariae as antigen. One hundred and eighteen sera collected from an area endemic for Bancroftian filariasis were tested. While 80% of sera from microfilariae carriers had no demonstrable antisheath antibodies, more than 80% of amicrofilaraemic samples (chronic filariasis cases and endemic normals) had antisheath antibodies. The antibody activity was found in IgG, IgM and also IgE isotypes. IgG subclass typing with monospecific antisera revealed significantly higher antisheath activity in IgG2 in comparison with other IgG subclasses. The determinants on sheathed microfilariae reacting with antisheath antibodies were found to be thermostable (100 degrees C for 30 minutes), resistant to protease treatment and significantly sensitive to sodium periodate treatment, indicating the possible role of carbohydrate moieties in eliciting protective antisheath antibodies in Bancroftian filariasis.     

Medical negligence or diagnostic conundrum? A medico-legal case study

India is a signatory to the UN backed Consumer Protection Resolution, and has enacted the Consumer Protection Act in 1986 to promote and protect the rights of consumers. A land-mark judgment of the Supreme Court of India in 1996, has paved the way for a number of lawsuits involving the public sector, including an eminent tertiary care medical institution. The case described in this study was filed with the State Consumer Dispute Redressal Commission in June 2000. The complainant was a fifty year old female who noticed a lump in her right breast; which was diagnosed as malignant by fine needle aspiration cytology (FNAC); and was treated by surgery and adjuvantradio-therapy (brachytherapy). Subsequently, the tissue sent for histo-pathological study was reported to be 'benign phyllodes tumour'; which was confirmed by other centres in India and the UK. The complaint filed for total damages amounting to Rupees 19 lacs (approx. 27,300 UK pounds) along with interest from the date of operation. Review of the relevant literature suggests that phyllodes tumour of the breast has various sub-types;and even borderline cases can develop malignancy at a later date. It is also clear that false positive cases had been reported previously in cases diagnosed by FNAC. Finally, avenues to minimise litigation through in-house mechanisms and a new concept of mediation have been explored.     

Protective immunity in human lymphatic filariasis: problems and prospects

Human filariasis caused by lymphatic dwelling nematodes, affecting 120 million persons worldwide, is a major public health problem. Efforts towards development of vaccines for such large tissue-dwelling nematodes depends significantly on identification and demonstration of protective immunity in the exposed population. Immunological studies conducted in human filariasis so far are essentially attempts to establish a correlation of the immune response phenotypes with presence or absence of filarial infections/disease in the host, and the cause-effect relationship between the observed immune responses in the host and protective immunity continues to be conjectural. This short review attempts to clarify the functional definition of protective immunity, problems associated with identification of putatively immune subjects in endemic areas, role of antibodies reactive to surface of microfilariae and larvae stages of filarial parasites and importance of undertaking immunological investigations on a longitudinal basis in different cohorts of subjects presenting with one or the features of infection and/or disease for more accurate delineation of protective immunity in human filariasis.