Comparison of assays for determination of peptide content for lyophilized thymalfasin*

Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

HIV AND TUBERCULOSIS CO-INFECTION IN A REFERRAL CHEST HOSPITAL

Serving personnel of Armed Forces admitted with tuberculosis between Apr 1996–1999 were evaluated for co-infection of tuberculosis and HIV. Sixty (1.06%) of tuberculosis patients were found to be HIV positive. Initial test was done by spot kits and subsequently confirmed by ELISA on two different samples. Majority of the cases were in sexually active age group 48 (80%). Alcohol and smoking was associated in 80% cases. Thirty six (60%) were sputum smear positive for AFB. Twenty eight (46.7%) gave history of exposure to sex workers. Family members were not available for study. Sero prevalence of HIV in association with tuberculosis is less in Armed Forces compared to civil population.KEY WORDS: HIV, Seroprevalence, Tuberculosis     

Epidemiological profile,management and outcomes of patients with acute coronary syndrome: Single centre experience from a tertiary care hospital in North India

BackgroundCardiovascular disease is the leading cause of death in India. Our aim is to study the clinical, epidemiological profile and in-hospital outcomes of patients presenting with acute coronary syndrome.MethodsWe did a prospective single center observational study of the 1203 patients presenting with ACS to a tertiary referral center in North India over a period of one year (July 2018–June 2019).ResultsThe mean age of study population was 58.4 ± 12.5 years. STEMI and NSTE-ACS accounted for 69.9% and 31.1% respectively. 62.1% of our patients were from rural background. The median time to hospital admission was 600 min for STEMI patients, thrombolysis was performed in 52% of cases. Cardiogenic shock at presentation was noted in 18%. Coronary angiography and percutaneous coronary intervention were done in 1062 (88.3%) and 733 (60.9%) patients respectively. The overall in-hospital mortality was 7.6%. STEMI patients had higher mortality than NSTE-ACS (8.9% vs 4.5% p < 0.001). Female gender (OR?3.306 C.I. 1.87–5.845), severe MR (OR?4.65, C.I.?1.187–18.18), acute kidney injury (AKI) at admission (OR-5.15, C.I.?2.5–10.63), higher Killip class (class III/IV) (OR?3.378,C.I.?1.292–8.849), AF (OR?3.25, C.I.?1,18–8.92), complete heart block (CHB) (OR?4.44,C.I.?2.09–9.43) and right bundle branch block (RBBB) (OR?2.86, C.I.?1.2–6.8) were significant predictors of in hospital mortality.ConclusionsOur study represents the predominance of STEMI as the initial ACS presentation with a considerable delay in first medical contact and higher prevalence of cardiogenic shock (CS). STEMI patients had higher mortality. Female sex, severe MR, AKI, higher Killips class, AF, CHB, RBBB being predictors of high in-hospital mortality in ACS patients.     

Biomarkers of senescence in non-human primate adipose depots relate to aging

Forty-three female African green monkeys (Chlorocebus aethiops sabaeus) were selected to represent young adult to advanced geriatric ages (7–24 years) to exhibit a wide range of obesity status (8–53% body fat) and diverse metabolic syndrome criteria such as diabetes, dyslipidemia, and hypertension. Subcutaneous and visceral adipose tissues were collected and evaluated for the presence of senescence cells in both whole tissue and single-cell isolates from subcutaneous sources, utilizing senescence-associated β-galactosidase (SAβ-gal) staining. Plasma samples were analyzed for selected metabolic and inflammatory biomarkers related to the senescence-associated secretory profile. Our results indicated that tissue staining scores did not differ between subcutaneous and intra-abdominal visceral depots and were highly related within individuals. Tissue staining was significantly associated with chronological age; however, no associations with fatness or metabolic syndrome criteria were observed. Associations with age were unchanged when obesity status was included in regression models. Isolated cell staining did positively relate to age but not tissue staining, suggesting some of the SAβ-gal-positive cells were stromal vascular cells or small adipocytes, but that mature large adipocytes, filtered out in the cell isolation process, are also likely to exhibit positive SAβ-gal staining. Plasminogen activator inhibitor-1 (PAI-1) concentration in circulation was the sole inflammation-related biomarker that positively associated with age and is considered to be a marker of senescent cell burden. Our study is the largest, most comprehensive assessment of adipose SAβ-gal staining in a relevant animal model of human aging, and confirms that this senescence-associated biomarker specifically indicates an age-related process.

     

Muramyl dipeptide: Not just another brick in the wall

The robust expression of microbial pattern recognition receptors such as TLR4 and Nod2 in intestinal stem cells reflects an active communication dynamic between the host and the gut microbiota. A new study reveals that muramyl dipeptide, the bacterial cell wall peptidoglycan motif, activates Nod2 within crypt base columnar Lgr5-positive stem cells and promotes their survival. Apart from the immediate relevance to the growth of organoids for in vitro experiments, the study raises new questions about the molecular mechanisms whereby gut microbes influence intestinal physiology.