Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

OBJECTIVE: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients. We wanted to see if there is a similar phenomenon for Mycophenolate in SSc. METHODS: Twenty SSc patients, who were on a stable dose of MMF (1.5-3 g) underwent a sequential cross over study with MMF alone in the first month, followed by co-treatment with Ranitidine and then Esomeprazole in the second and third month respectively. Estimation of 12-hour area under curve (AUC) of Mycophenolic Acid (MPA) levels and total GI score were calculated at the end of each month and compared between the treatment arms. [Trial registration: CTRI/2020/06/025,939] RESULTS: Co-administration of esomeprazole was associated with 32.7% (mean difference = 22.28 µg h ml-1) reduction in mean AUC MPA, whereas ranitidine caused a reduction of 21.97% (mean difference = 14.93 µg h ml-1) in MPA AUC when compared to MMF without anti-acid therapies. The addition of ranitidine or esomeprazole resulted in significant reduction in the total GI score. CONCLUSION: Co-administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with SSc. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents are co-prescribed with MMF.

Antibody responses after documented COVID-19 disease in patients with autoimmune rheumatic disease.

Patients with autoimmune rheumatic diseases (AIRD) are suspected to have less robust immune responses during COVID-19 due to underlying immune dysfunction and the use of immune-suppressive drugs. Fifty consecutive patients with a diagnosis of AIRD on disease-modifying drugs were included at around 30 days after a confirmatory test for COVID-19. Fifty controls matched one to one for age, sex, and severity of COVID-19 were also included at around 30 days after testing positive for COVID-19. Antibody titers for anti-spike protein IgG and anti-nucleocapsid protein IgG were estimated. Cases (mean age 45.9 ± 13; 76% females) and controls (mean age 45.9 ± 13; 76% females) had similar proportion of comorbidities. Of the cases, 4 had moderate and 1 had severe COVID-19, while 3 and 1 of controls had moderate and severe COVID-19 respectively. Positivity of anti-N IgG was similar between patients (80%) and controls (90%) (p = 0.26). Similarly, anti-S IgG was positive in 82% of patients and 86% of controls (p = 0.79). Both the antibodies were negative in seven (14%) patients and five (10%) of controls (p = 0.76, Fischer exact test). Only anti-N IgG titers were lower in patients as compared to controls. In four patients with rheumatoid arthritis, two with spondyloarthritis and one with eosinophilic fasciitis both antibodies were not detectable. They did not differ from the rest of the cohort in clinical characteristics. The patients with AIRD had adequate protective antibody responses to COVID-19 at a median of 30 days post-infection. Thus, the presence of AIRD or the use of immunosuppressants does not seem to influence the development of humoral immune response against COVID-19. Key Points • Patients with autoimmune rheumatic diseases (AIRD) are suspected to have less robust immune responses. • In our cohort of 50 patients with AIRD with confirmed COVID-19, only seven did not have detectable protective antibodies at 30 days post infection. • Patients with AIRD on immunosuppressants have adequate protective antibodies post COVID-19 disease, at rates similar to that in health controls.

Self-Care Interventions That Reduce Hospital Readmissions in Patients With Heart Failure; Towards the Identification of Change Agents.

Unplanned hospital readmissions are the most important, preventable cost in heart failure (HF) health economics. Current professional guidelines recommend that patient self-care is an important means by which to reduce this burden. Patients with HF should be engaged in their care such as by detecting, monitoring, and managing their symptoms. A variety of educational and behavioural interventions have been designed and implemented by health care providers to encourage and support patient self-care. Meta-analyses support the use of self-care interventions to improve patient self-care and reduce hospital readmissions; however, efficacy is variable. The aim of this review was to explore methods to achieve greater clarity and consistency in the development and reporting of self-care interventions to enable 'change agents' to be identified. We conclude that advancement in this field requires more explicit integration and reporting on the behaviour change theories that inform the design of self-care interventions and the selection of behaviour change techniques. The systematic application of validated checklists, such as the Theory Coding Scheme and the CALO-RE taxonomy, will improve the systematic testing and refinement of interventions to enable 'change agent/s' to be identified and optimised.

Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II.

Mucopolysaccharidoses (MPS), a subgroup of lysosomal storage disorders, are caused due to deficiency of specific lysosomal enzyme involved in catabolism of glycosaminoglycans. To date more than 200 pathogenic variants in the alpha-l-iduronidase (IDUA) for MPS I and ∼500 pathogenic variants in the iduronate-2-sulphatase (IDS) for MPS II have been reported worldwide. The mutation spectrum of MPS type I and MPS type II disorders in Indian population is not characterized yet. In this study, we carried out clinical, biochemical, molecular and in silico analyses to establish the mutation spectrum of MPS I and MPS II in the Indian population. We conducted molecular analysis for 60 MPS-affected patients [MPS I (n = 30) (Hurler syndrome = 17, Hurler-Scheie syndrome = 13), and MPS II (n = 30) (severe = 18, attenuated = 12)] and identified a total of 44 [MPS I (n = 22) and MPS II (n = 22)] different pathogenic variants comprising missense, nonsense, frameshift, gross deletions and splice site variants. A total of 20 [MPS I (n = 14), and MPS II (n = 6)] novel pathogenic sequence variants were identified in our patient cohort. We found that 32% of pathogenic variants detected in IDUA were recurrent and 25% in MPS II. This is the first study revealing the mutation spectrum of MPS I and MPS II patients in the Indian population.

Granulosa cell tumor of the ovary--an incidental finding during caesarean section--a rare case report.

Approximately one-fourth of the ovarian neoplasms and cysts are diagnosed incidentally during caesarean section. The possibility of borderline tumor or cancer should be considered although existence of ovarian malignancy in pregnancy is rare. We report a case of a rare solid malignant tumor of the ovary incidentally found during caesarean section. Intraoperatively, it was thought to be a variant of the common ovarian teratoma. Ovariectomy was done but histopathology revealed it to be granulosa cell tumor. The diagnosis changed the prognosis and future treatment plan drastically. Equipped with this knowledge physicians can be made aware of the existence of this little-known ovarian neoplasm along with its rare association with pregnancy. Also one can better manage, counsel and follow-up the patients after delivery, given the knowledge of the tumours' inevitable malignant potential and its high incidence of recurrence.

Effects of chlorpromazine on the enzymatic and toxic properties of the most basic phospholipase A2 from Vipera russelli snake venom.

The effect of chlorpromazine on various biological activities of phospholipase A2 VRV-PL-VIIIa from Vipera russelli snake venom was investigated. The drug inhibited the in vitro phospholipase A2 activity of the enzyme by 55%. The ID50 was found to be 1.15 microM. Increasing substrate concentration relieved the inhibition of phospholipase A2 activity by the drug indicating probable interaction with the substrate. The drug totally quenched the fluorescence intensity of the enzyme. Chlorpromazine increased the LD50 of the enzyme by 1.6 fold. The drug also inhibited hemolytic and anticoagulant potencies but failed to inhibit edema inducing activity and myotoxicity of the enzyme.

Primary structure of a cytotoxin-like basic protein from Naja naja naja (Indian cobra) venom.

The complete amino acid sequence of a cytotoxin-like basic protein (CLBP) from the venom of Naja naja naja (Indian Cobra) was determined by manual degradation using a 4-dimethylaminoazobenzene-4'-isothiocyanate double-coupling method. Peptide fragments obtained by chemical cleavage with cyanogen bromide and enzymic cleavages with trypsin and Staphylococcus aureus proteases for sequence analysis were purified by reversed-phase chromatography. The total number of amino acid residues was 61, with leucine as the C-terminal residue.

Dissociation of enzymatic activity from toxic properties of the most basic phospholipase A2 from Vipera russelli snake venom by guanidination of lysine residues.

The most basic phospholipase A2 VRV-PL-VIIIa purified from Russell's viper venom is a toxic enzyme. It induced neurotoxicity, myotoxicity, and oedema and was lethal to mice at 5.3 micrograms/g body weight. It also inhibited the coagulation of the human plasma. The epsilon-amino groups of lysine residues of the toxic enzyme VRV-PL-VIIIa were guanidinated with o-methylisourea. Guanidination of the enzyme did not alter the enzymatic activity markedly. The guanidinated enzyme became non-lethal in doses up to 16 micrograms/g body weight, and failed to elicit neurotoxic symptoms in experimental animals and oedema in the foot pads of mice. Also, its myotoxic and anticoagulant potencies were decreased significantly.

Effects of chemical modification on enzymatic and toxicological properties of phospholipases A2 from Naja naja naja and Vipera russelli snake venoms.

The effects of chemical modification with 4-NN-dimethyl amino azo benzene-4'-isothiocyanate on various biological activities of phospholipases A2, NN-XIII-PLA2 from Naja naja naja and VRV-PL-VIIIa from Vipera russelli snake venoms were investigated. Modification of the enzymes resulted in significant reduction of lethal, hemolytic, anticoagulant and enzymatic activities. The Km value of the modified enzymes was increased. The modified enzymes failed to induce edema in the foot pads of mice and were non-lethal up to 16 mg/kg body weight. However, considerable myotoxicity was retained, suggesting that the toxins have multiple sites for biological activities. The aggregated form obtained from modified NN-XIII-PLA2 exhibited decreased enzymatic activity and increased toxicity compared to the modified monomer. This aggregated form did not show pyrophosphatase/phosphomonoesterase activity in contrast to the aggregated form obtained from the native NN-XIII-PLA2 molecule.