Comparative Evaluation of Angiotensin-Converting Enzyme Inhibitors for their Beneficial Effects in Patients with Ischemic LV Systolic Dysfunction and Undergoing Coronary-Artery Bypass Surgery.

We compared three angiotensin-converting enzyme (ACE) inhibitors, captopril, perindopril, and ramipril, in the presented prospective study for their effectiveness in patients having left ventricular (LV) systolic dysfunction and undergoing coronaryartery bypass grafting (CABG). We enrolled 27 patients in captopril, 43 patients in perindopril, and 70 patients in ramipril group. There was about 25%–36% rise in LVEF after 3 and 6 months of ACE inhibitor administration in all three groups. The reduction in LV diameters did not differ significantly amongst the three groups. There was a significant decrease (p < 0.05) in LV end-diastolic diameter from baseline levels in captopril and perindopril groups after 3 months that got increased after 6 months but remained below pretreatment levels in both the groups. In ramipril group, there was no much change in this parameter from baseline levels at 3 and 6 months of treatment. After 6 months of treatment, the percent reduction in LV end-systolic diameter was also sustained in perindopril-treated patients. The percent reduction was greater in the perindopril group (3 and 6 months: 7.39 ± 5.94 and 7.73 ± 3.43, respectively) as compared to that observed in captopril group (3 and 6 months: 5.67 ± 1.05 and 2.52 ± 3.11, respectively) and ramipril group (3 and 6 months: 7.30 ± 2.75 and 4.93 ± 3.22, respectively). Mitral-valve regurgitation was greatly reduced in the captopril group at 3 as well 6 months of ACE inhibitor administration. However, the percent reduction from baseline levels was not statistically significant amongst the three groups. The percent improvement in functional status was significantly greater in the ramipril treatment group (36.46 ± 3.14) after 6 months of treatment as compared to that of captopril (6.67 ± 10.64) and perindopril (4.17 ± 2.73) group. In conclusion, our data show equal beneficial effects with all three ACE inhibitors under investigation in CABG patients with LV systolic dysfunction, with marginal superiority for perindopril.

Sub-biochemical hypothyroidism: an exaggerated thyroid stimulating hormone response to thyrotrophin releasing hormone.

BACKGROUND: The availability of sensitive and specific assays for evaluation of the thyroid axis has allowed definition of thyroid disorders at subclinical stage. This has almost obviated the use of thyrothrophin releasing hormone (TRH) study. We describe here a group of patients with minimal signs of hypothyroidism having normal thyroid function tests (T3, T4, thyroid stimulating hormone (TSH)) and have shown exaggerated TSH response to TRH. MATERIAL AND METHODS: Total 82 subjects were studied. Of these, 11 were age and sex matched controls, and 71 were patients. In all subjects TSH and other thyroid assays (T3, T4, FT4) were done by immunoradiometric assay (IRMA), and radioimmunoassay (RIA) respectively. Thyroid antibody was carried out by haemagglutination method. Results were compared to age and sex related normal ranges. To further investigate the status of thyroid axis, TRH study was carried out using standard protocol. RESULTS: Based on TRH study patients were grouped in three categories. Group 1 included 29 patients whose TSH response to TRH was normal. Group 2 included 20 patients with normal baseline TSH and exaggerated TSH response to TRH and Group 3 included 18 patients with baseline TSH in the range of 5 to 10 mu IU/ml and exaggerated TSH response to TRH. There was a significant difference to total T3 between group 1 and 3 (p < 0.05) but mean values were within normal limits. While no significant difference was observed in total T4 between controls and patient's group. Serum TSH values were high in group 3 as compared to controls and Group 1 and 2 (p < 0.0001). For Free T4 no statistical significance was observed between Group 1, 2 and 3. Thyroid antibodies were positive in 22.7% of patients in Group 2 and 33.33% in Group 3. CONCLUSION: We conclude from the present study that even with sensitive TSH assays TRH study still has a role to mark the early stage of hypothyroidism. Those with a normal or upper normal TSH with exaggerated response to TRH are termed as sub-biochemical hypothyroidism and can be considered for thyroid replacement therapy.

IDPH-8261--a new nonsteroidal antiinflammatory agent.

IDPH-8261, methyl alpha-methyl-4-(3-thienyl)benzeneacetate, exhibited marked anti-inflammatory activity in acute, subacute and chronic models of inflammation. In rats, IDPH-8261 exhibited a dose related inhibition of carrageenin-induced rat paw edema and the inhibition was greater than ibuprofen, phenylbutazone, but was three times less than indomethacin. It exhibited anti-inflammatory activity in normal and adrenalectomized rats. It also exhibited the activity against various phlogistic agents. IDPH-8261 exhibited AI activity in subacute granuloma tests. In adjuvant-induced established polyarthritis. IDPH-8261 exhibited anti-arthritic effect at a very low dose (ED50 = 4 mg/kg, p.o.). Ulcerogenic liability was the lowest (UD50 = 180 mg/kg, p.o.), when compared to reference standard drugs. Low toxicity and high efficacy may make this compound a potentially useful therapeutic agent.

Prevalence of microalbuminuria in diabetic subjects.

Total 193 diabetic patients were investigated to assess the prevalence of microalbuminuria. Urinary albumin excretion rate (UAER) was measured by radioimmunoassay (RIA) on 3 hours urine samples. The prevalence of microalbuminuria (UAER) > 15 micrograms/min was 41%. Microalbuminuria was commonly observed in patients having diabetes for more than 5 years. A significant correlation was found between duration of diabetes and microalbuminuria (p < 0.01). Glycemic control (fasting and postprandial blood sugar) did not show any correlation with UAER, whereas blood urea (r.39, p < 0.01), creatinine (r.26, p < 0.05) and chloride (r.24, p < 0.05) were positively correlated. A significant correlation was found between raised blood pressure and UAER (p < 0.01).

Action of some amides of substituted ethylenediamines on central nervous system.

Five of the substituted ethylenediamine amides (LMG I to V) were tested for various CNS attributes and for acute toxicity (24 hr mortality). All compounds were potent analgesics in various animal tests, LMG V being most potent. All reduced spontaneous activity of mice and potentiated ether anaesthesia. However, CAR was not altered and anti-MES were not pronounced in rats. Compounds appear to have a wide safety margin considering ED50 and LD50 in mice.

Pharmacological studies of certain amides of substituted ethylenediamines - I.

Five substituted amides of ethylenediamines produced hypotension in dogs, which was not blocked by atropine, mepyramine and propranolol. The amides potentiated the pressor responses to Adr and NA and antagonised the depressor responses to Ach and histamine. The compounds also antagonised Ach-induced contractions on the frog rectus abdominis muscle and of carbachol on rat isolated colon suggesting d-tc and atropine-like actions respectively. Antihistaminic activity was observed on guinea pig isolated ileum as on dog blood pressure. Adr and NA-induced relaxation of rabbit isolated jejunum was potentiated. Finally Adr and NA-induced contractions of rat isolated seminal vesicle was antagonised.