Structure and conformation of peptides involving prolyl residue III. L-Prolyl-L-isoleucine monohydrate

The dipeptide, L-prolyl-L-isoleucine monohydrate (C₁₁ H₂₀N₂O₃· H₂O, molecular weight 246.3) crystallizes in the monoclinic space group P2₁, with a = 6.601(3)Å, b = 5.413(3) Å, c = 19.128(6) Å, β= 98.1(1)°, Z = 2, Do = 1.20g·cm^-3 and Dc = 1.208g·cm^-3. The structure was solved by MULTAN–80 and refined to a final R-factor of 0.081 for 594 reflections measured on a Enraf Nonius CAD-4 diffractometer. The peptide linkage exists in the trans conformation. The pyrrolidine ring is disordered with two alternate envelope conformations for the C^γ atom. The values of the sidechain torsion angles are: χ₁₁=– 63.6(17)°, χ₁₂= 171.1(16)° and χ₂=– 59.6(21)° for isoleucine (C-terminal). The crystal structure is stabilized by a three-dimensional network of N—H ? O, O—H ? O and C—H ? O hydrogen bonds. The dipeptide exists in the extended Conformation.     

Obstructive Sleep Apnoea: From pathogenesis to treatment: Current controversies and future directions

Obstructive sleep apnoea (OSA) is a common disease, recognized as an independent risk factor for a range of clinical conditions, such as hypertension, stroke, depression and diabetes. Despite extensive research over the past two decades, the mechanistic links between OSA and other associated clinical conditions, including metabolic disorders and cardiovascular disease, remain unclear. Indeed, the pathogenesis of OSA itself remains incompletely understood. This review provides opinions from a number of leading experts on issues related to OSA and its pathogenesis, interaction with anaesthesia, metabolic consequences and comorbidities, cardiovascular disease, genetics, measurement and diagnosis, surgical treatment and pharmacotherapeutic targets.     

Low-dose recombinant interferon therapy in anti-HBe-positive chronic hepatitis B in Asian Indians*

Approximately 15% of Indian patients with hepatitis B virus (HBV)-related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant-related CLD in Asian Indians. Eighteen patients (mean age 38.2 ± 12 years, M: F: 17: 1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti-HBe positive, HBV-DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV-DNA (both by dot-blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV-DNA by dot-blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 ± 12 vs 55 ± 29 IU/L, P < 0.01) and the histological activity index (15 ± 1.4 vs 12 ± 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 ± 0.4 g/dL vs 3.8 ± 0.4 g/dL, P= 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV-DNA positive at the end of follow up. This study concluded that: 1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant-related chronic liver disease in Asian Indians. 2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate. 3. Prolonged low-dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.     

固定衬垫式和活动衬垫式全膝人工关节置换术后随访4．5年以上的对比性研究

背景：低接触应力旋转平台（活动衬垫式）和Insall Burstein-Ⅱ型（固定衬垫式）全膝人工关节假体各自独立的长期稳定性已有报道，但我们尚未见有关这两种假体的中长期随访及对比性研究。 方法：对32例双侧膝关节畸形和术前活动范围均相似的膝关节炎患者进行了前瞻性评估，患者同意一侧膝关节行活动衬垫全膝关节置换，另一侧膝关节行固定衬垫全膝关节置换。术后平均随访6年，使患者、医生和观测者的相关干扰降至最小，对两种假体进行对比分析，项目包括临床和X线片结果、生存率和并发症发生率。 结果：术后骨关节炎患者的功能评分和活动范围好于类风湿性关节炎患者。然而，对患者在膝关节协会评分、屈曲范围、主观表现或髌股并发症发生率等方面进行评估，没有发现活动衬垫式假体比固定衬垫式假体更好。X线片显示两者在假体排列上没有差异。两例使用活动衬垫式假体的膝关节需要再次手术，其中1例因衬垫脱位而需要早期翻修，另1例因深部感染而进行关节融合。 结论：我们发现中期随访患者的临床表现显示，活动衬垫式全膝关节置换术并不比固定衬垫式全膝人工关节置换术具有更多的优点。活动衬垫式假体发生假体脱位和半脱位的危险性应给予重视，在发生脱位后要早期进行翻修。 可信水平：治疗性研究，Ⅱ级，进一步可信度参见作者介绍。     

Changing Trends in Acute Renal Failure in Third-world Countries -- Chandigarh Study

The pattern of acute renal failure in third-world countriesis changing albeit at a slower pace compared to that in developedcountries. Of the 1862 patients with acute renal failure requiringdialysis between 1965 and 1986 in a north Indian centre, 60,15 and 25 per cent were related to medical, obstetrical andsurgical conditiom respectively. Among the medical patients,diarrhoea1 diseases which caused 23 per cent of the total numberof cases of acute renal failure in the period 1965 to 1974 causedonly 10 per cent in 1981 to 1986. In the same period, acuterenal failure due to sepsis and drugs increased while that dueto copper sulphate poisoning and intravascular haemolysis showeda downward trend. Obstetrical acute renal failure declined from22 per cent in 1965 to 1974 to 9 per cent during the period1981 to 1986. This decline was chiefly due to a fall in casesof septic abortion, puerperal sepsis a d postpartum haemorrhage.Surgical acute renal failure increased from 11 per cent duringthe period 1965 to 1974 to 31 per cent in the 1980s, predominantlydue to an increase in patients with obstructive uropathy. Despitethese favourable trends, the pattern of acute renal failurein the third world continues to be different from that in thedeveloped countries.     

Abuse of codeine-containing cough syrups: a report from India

Aim. To study the socio-demographic and clinical profile of patients seeking treatment for abuse of codeine-containing cough syrups (CCS). Design. Observational; case series. Setting. An addiction clinic in North India. Participants. Forty-six consecutive treatment-seeking patients of DSM-III-R-diagnosed dependence on CCS, from January 1994 to June 1995. Measurements. Semi-structured interview schedule for patients and their family covering socio-demographic and clinical variables. Findings. All patients were male. Many were young (mean age 27 years), with completed school education (85%) and from urban backgrounds (80%). The mean age of starting CCS use was 23 years. Initiated commonly through friends (89%) and often for curiosity (63%), 89% of the patients progressed to daily use of CCS in less than 6 months (54% in less than a month), and in quantities much higher than prescribed limits. Opioid-like withdrawal was reported by 92%. Concurrent use of other substances, psychiatric co-morbidity and HIV-related risk behaviour were present in 72%, 24% and 45%, respectively. Most of the patients reported a ‘stimulant’ effect of CCS (‘alert’, 96%; ‘more active’, 94%). Conclusions. The combination of an opioid and a sympathomimetic agent in the CCS may cause a special, distinct euphoretic effect. This effect, along with the low price, easy availability and ‘pure’ preparation of CCS, may be responsible for the rapidly rising popularity of the CCS as drugs of abuse in India.     

Hormone Profiles at High Altitude in Man

Altitude induced alterations in circulatory levels of PRL, LH, FSH and testosterone were studied in seven eugonadal men at sea level (SL), during their stay at high altitude (HA, 3500 m) and a week after return to SL. The mean plasma PRL level at SL was 5.83 +/- 1.7 SE ng/ml. On day one and seven of arrival at HA, the PRL values of 7.81 +/- 1.81 and 9.21 +/- 1.64 ng/ml respectively were not significantly different (p greater than 0.05) than the initial SL values. However, on day 18 of stay at HA, PRL levels were significantly increased (p less than 0.01) to 17.68 +/- 1.82 ng/ml and returned to initial SL values within seven days of return to SL. A significant decrease (p less than 0.01) in LH and testosterone was observed on seventh day of stay at HA and the decreased levels were maintained till day 18 of observations. Plasma testosterone returned to the initial SL values within a week of return to SL, whereas LH levels remained significantly lower (p less than 0.01). The FSH levels did not show any significant change during their stay at HA or after return to SL. These observations suggest that exposure to altitude is associated with hyperprolactenemia and an impaired pituitary gonadal function. The decreased levels of LH and testosterone at HA could either be due to hypoxic stress per se or secondary to altitude induced hyperprolactenemia.     

Pattern of Alcohol-related Liver Disease in Dependant Alcoholics: the Indian dimension

To study the incidence and profile of alcoholic liver disease in dependant alcoholics, 56 patients, 31 with moderate and 25 with severe dependence on alcohol, were assessed by a severity of alcohol dependence questionnaire. All the patients were males. Forty-five (80.4%) dependant alcoholics were found to have alcoholic liver disease, diagnosed either by abnormal biochemical tests (78.6%) or when available, specific histological lesions (87.8%). Of the 49 (87.5%) patients in whom liver biopsy could be obtained, fatty liver was seen in 17 (34.7%), hepatitis in 22 (44.9%) and cirrhosis in four (8.2%) patients. Liver biopsy was normal in the remaining six (12.2%) patients. Symptoms suggestive of alcoholic liver disease were however, observed in only 18.6% patients. No significant difference was seen in the nature and severity of biochemical and histological liver injury between patients with moderate or severe dependence on alcohol. It can be concluded that significant hepatic abnormalities exist in a high percentage of dependant alcoholics in India. Increased awareness and institution of measures for early screening of these patients for the presence of underlying liver disease are warranted.