Serum Magnesium Level and It's Relation in Predicting Adverse In-Hospital Outcome in Patients with First Attack of Myocardial Infarction.

Acute myocardial infarction (AMI) patients characterize a large proportion of admissions in coronary care unit and their management and risk stratification is of immense importance. Hypomagnesemia is a long-term risk factor for incident of both myocardial infarction and arrhythmia. We assessed whether serum magnesium levels at admission is associated with arrhythmias and in-hospital mortality in patients with acute myocardial infarction (AMI). The aim of the study was to evaluate the prognostic implications of serum magnesium level in patients with acute myocardial infarction. This cross-sectional observational study was conducted in the department of cardiology in Mymensingh Medical College Hospital from October 2017 to March 2019. Total 259 acute myocardial infarction patients were included considering inclusion and exclusion criteria. The sample population was divided into two groups: Group-I: Patients with acute myocardial infarction with serum magnesium ≥1.82mg/dl. Group-II: Patients with acute myocardial infarction with serum magnesium <1.82mg/dl. Serum magnesium level was measured on admission, and the incidence of in-hospital major cardiac events was assessed. In this study mean serum magnesium level of Group-I, Group-II were 2.21±0.14mg/dl, 1.60±0.15mg/dl respectively. It was statistically significant (p<0.05). In-hospital outcomes of the study group revealed that low risk group patients were uneventful outcome during hospitalization period, they had no any complication. In Group-I patient, 9(4.8%) were developed arrhythmias, 26(13.9%) were developed heart failure, 9(4.8%) were developed cardiogenic shock and 3(1.6%) were died and in Group-II patient, 44(61.10%) developed arrhythmias, 9(12.50%) were developed heart failure, 7(9.7%) were developed cardiogenic shock and 12(16.7%) were died out of them which was statistically significant (p<0.05). Mean duration of hospital stay of the study population according serum magnesium level was in Group-I, 4.27±0.68 days, in Group-II, 5.84±1.05 days which was statistically significant (p<0.05). In conclusion patient with serum magnesium level less than 1.82mg/dl increased the risk of in-hospital arrhythmia and death.

Association of Body Mass Index with Angiographic Severity of Coronary Artery disease in patients with Acute Coronary Syndrome.

Coronary artery disease (CAD) is the leading cause of death in developed and developing countries. Associated co-morbidities like diabetes, hypertension and obesity are making the situation worse. WHO enlisted obesity as an epidemic which also affects a great number of young population. Some recent studies showed the presence of an apparent paradoxical relationship between obesity and cardiovascular prognosis in certain subsets of patents. As BMI is an established marker of obesity; an attempt has been made to assess relationship between BMI and angiographic severity of coronary artery disease in Acute Coronary Syndrome (ACS) patients of Bangladeshi origin. To assess the association between body mass index and angiographic severity of coronary artery disease in patients with acute coronary syndrome; this cross sectional analytical study was conducted in the Department of Cardiology, Mymensingh Medical College Hospital (MMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU) from December 2016 to February 2018 among purposively selected 65 patients. Relevant ethical issues were taken into consideration. Coronary angiogram was done in the same index hospitalization period. After coronary angiogram performed patients were grouped into two groups according to their BMI. Patients with BMI <25kg/m² as Group I and those ≥25kg/m² as Group II. Angiographic severity of coronary artery disease was assessed by vessel score and Syntax score. Mean age of Group I was 54.45±10.42 years, while in Group II it was 50.76±8.89 years reflecting the early presentation of higher BMI patients. Male to female ratio was 12:1. Mean BMI of Group I and Group II was 22.56±1.59 and 28.67±2.64 respectively. In Group I, 10(25.0%) had single vessel lesion, 15(37.5%) had double vessel lesion and 14(35.0%) had triple vessel lesion, while in Group II, 6(24.0%) had single vessel lesion, 12(48.0%) had double vessel lesion and 5(20.0%) had triple vessel lesion. Mean Syntax score of Group I and Group II was 13.18±8.45 and 10.42±7.14 respectively. Patients in the increasing BMI class had a higher prevalence of diabetes, hypertension and dyslipidaemia. A negative correlation was observed between BMI and angiographic severity (Vessel score, Syntax score and HRCA e.g. LM disease) of CAD indicating that patients with higher BMI had a lower coronary artery disease (CAD) severity than their normal BMI counterparts. Patients with high BMI have a lower CAD severity than usually expected. After adjustment for co-morbidities, BMI was not found as an independent predictor of severity of coronary artery disease.

Label-free quantitative proteomics reveals molecular correlates of altered biomechanical properties in molar incisor hypomineralization (MIH): an in vitro study.

PURPOSE: Molar-incisor hypomineralization (MIH) is a qualitative developmental defect of enamel that affects first permanent molars with or without affecting permanent incisors. We aimed to carry out a quantitative proteomics-based study to compare and evaluate proteins in sound and MIH-affected enamel. MATERIALS AND METHODS: Ten blocks each of the MIH-affected enamel and sound enamel were processed and prepared for LC-MS/MS analysis. Label-free quantitation was carried out to evaluate the differentially expressed proteins in the two groups of samples. RESULTS: A significant increase in the number of proteins in MIH-affected enamel (50.3 ± 29.6) was observed compared to the sound enamel (21.4 ± 3.2). While proteins like collagens, α1-anti-trypsin, kallikrein-4 (KLK4), matrix metalloprotease-20 (MMP-20), alpha-2-macroglobulin, and alpha-2-HS-glycoprotein were upregulated in sound enamel, there was over-expression of albumin, calcium-binding proteins, anti-thrombin III, and dentin sialophosphoprotein (DSPP), along with proteins implicated in stress response and inflammatory processes in MIH. CONCLUSION: We propose that altered biomechanical properties of the enamel in MIH samples arise due to (i) down-regulation of proteins contributing to collagen biosynthesis and fibril formation; (ii) an overall imbalance in required levels of proteases (KLK4 and MMP-20) and anti-proteases (anti-thrombin-III which inhibits KLK-4), essential for optimal mineralization; (iii) very low levels of alpha-2-macroglobulin with important consequences in enamel mineralization and amelogenesis; and (iv) increased albumin in MIH, preventing proper growth of hydroxyapatite crystals. Increased inflammatory component was also seen in MIH; however, whether inflammation is a cause or consequence of the poor mineralization process needs to be assessed.

Relationship of Plasma Vitamin-D Level with Left Ventricular Ejection Fraction in Patients with First Attack of Acute Myocardial Infarction.

It has been widely reported that vitamin D deficiency is associated with Coronary heart disease (CHD), especially acute Myocardial infarction (MI). Many factors are responsible for reduced Left ventricular ejection fraction (LVEF) and acute Left ventricular fraction (LVF) after acute MI. This cross sectional descriptive type of study was conducted in the Cardiology department of Mymensingh Medical College Hospital from October 2017 to March 2019 to investigate the relationship of plasma vitamin D with LVEF in patients with first attack of acute MI. Total 185 patients of first attack of acute MI were included considering inclusion and exclusion criteria. Fasting blood samples were analyzed for plasma vitamin D level. Sample population were grouped at first into two, normal and low vitamin D level, taking 30ng/ml as cut-off value, low vitamin D level is further subdivided into insufficiency (21-29ng/ml), deficiency (10-20ng/ml) and severe deficiency (<10ng/ml). LVEF among the patients was observed. LVEF was found 49.88±8.58% patients having normal vitamin D level (>30ng/ml), 47.60±8.24% of patients having vitamin D insufficiency (21-29ng/ml), 44.38±8.12% of patients having vitamin D deficiency (10-20ng/ml) and 40.61±8.64% patients having severe vitamin D deficiency (<10ng/ml), which was statistically significant (p<0.05). So, low plasma vitamin D level is associated with reduced LVEF in patients hospitalized with first attack of acute MI.

Correlation of Mean Platelet Volume with ST Segment Resolution after Thrombolytic Therapy in Patients with ST Elevation Myocardial Infarction.

Acute occlusive thrombosis of the coronary artery is the principal cause of myocardial infarction where platelets play an important role. Large size platelets, easily measured by mean platelets volume (MPV) are thrombogenic and commonly seen after ST-segment elevation myocardial infarction (STEMI). ST segment resolution has been shown as a simple non-invasive marker that reflects both epicardial and myocardial reperfusion following thrombolysis. The present study intended to investigate whether MPV on admission correlated with ST segment resolution following thrombolysis in STEMI patient. This cross-sectional analytical study was conducted in the department of cardiology, Mymensingh Medical College and Hospital (MMCH), Mymensingh, Bangladesh from December, 2016 to June, 2018. Total 284 patients with first attack of STEMI were included after considering inclusion and exclusion criteria. Sample population was divided into two groups, Group I - Patients with successful ST segment resolution (≥50%). Group II - Patients with impaired ST segment resolution (<50%). MPV on admission was estimated during estimation of Complete Blood Count (CBC) by Automated Haematology Analyzer & compared between two groups. Successful ST segment resolution (≥50%) was seen in 67% of patients after thrombolysis. Admission MPV was higher in patients with impaired ST segment resolution (<50%) group than patients with ≥50% ST-segment resolution group (12.42±0.89fl vs.10.35±0.77fl respectively, p=0.001). Statistically significant strong negative correlation between MPV and ST segment resolution percentage (r = -0.742, p=0.001) suggesting that the higher the level of MPV, the lower the ST segment resolution percentage in first attack of STEMI patients. Multivariate regression analysis found MPV level on admission as an independent predictor of ST segment resolution. The study concluded that high MPV on admission correlate with impaired ST segment resolution following thrombolysis in STEMI patients.

Serum Albumin Level and In-Hospital Outcome of Patients with First Attack Acute Myocardial Infarction.

Acute myocardial infarction (AMI) patients constitute a large proportion of admissions in coronary care unit and their management and risk stratification is of immense importance. A decrease in serum albumin concentration might be associated with an increased risk in the incident of both cardiovascular diseases and worse hospital outcome. We assessed whether serum albumin levels at admission was associated with in-hospital adverse outcome in patients with first attack of acute myocardial infarction (AMI). The aim of the study was to evaluate association of serum albumin level with in-hospital outcome in patients with first attack of acute myocardial infarction. This cross-sectional analytical study was conducted in the department of cardiology in Mymensingh Medical College Hospital, Mymensingh, Bangladesh from March 2017 to February 2018. Total 374 patients of first attack of acute myocardial infarction included considering inclusion and exclusion criteria. The sample population was divided into two groups: Group I (Patients with acute myocardial infarction with serum albumin <3.5gm/dl) and. Group II (Patients with acute myocardial infarction with serum albumin ≥3.5gm/dl). Serum albumin level was measured within 24 hours of admission and the incidence of in-hospital major cardiac outcomes was observed. In this study mean±SD serum albumin level of Group I, Group II were 3.02±0.12gm/dl, 4.48±0.50gm/dl respectively. In Group I patient, 52(59.80%), 7(8.00%), 10(11.50%), developed heart failure, cardiogenic shock, arrhythmias respectively and 8(9.20%) died and in Group II patient 20(7.90%), 7(2.80%), 8(3.20%) developed heart failure, cardiogenic shock, arrhythmias respectively and 4(1.60%) died out of them and all of these outcome were statistically significant. Mean±SD duration of hospital stay of the study population according serum albumin level, in Group I, 5.76±1.83 days, in Group II, 4.40±1.22 days which was statistically significant (p<0.05). In conclusion, patient with first attack of acute myocardial infarction serum albumin level below 3.50gm/dl increased the risk of worse in-hospital outcome.

TAp73 loss favors Smad-independent TGF-ß signaling that drives EMT in pancreatic ductal adenocarcinoma.

Advances made in pancreatic cancer therapy have been far from sufficient and have allowed only a slight improvement in global survival of patients with pancreatic ductal adenocarcinoma (PDA). Recent progresses in chemotherapy have offered some hope for an otherwise gloomy outlook, however, only a limited number of patients are eligible because of important cytotoxicity. In this context, enhancing our knowledge on PDA initiation and evolution is crucial to highlight certain weaknesses on which to specifically target therapy. We found that loss of transcriptionally active p73 (TAp73), a p53 family member, impacted PDA development. In two relevant and specific engineered pancreatic cancer mouse models, we observed that TAp73 deficiency reduced survival and enhanced epithelial-to-mesenchymal transition (EMT). Through proteomic analysis of conditioned media from TAp73 wild-type (WT) and deficient pancreatic tumor cells, we identified a secreted protein, biglycan (BGN), which is necessary and sufficient to mediate this pro-EMT effect. Interestingly, BGN is modulated by and modulates the transforming growth factor-ß (TGF-ß) pathway, a key regulator of the EMT process. We further examined this link and revealed that TAp73 impacts the TGF-ß pathway by direct regulation of BGN expression and Sma and Mad-related proteins (SMADs) expression/activity. Absence of TAp73 leads to activation of TGF-ß signaling through a SMAD-independent pathway, favoring oncogenic TGF-ß effects and EMT. Altogether, our data highlight the implication of TAp73 in the aggressiveness of pancreatic carcinogenesis through modulation of the TGF-ß signaling. By suggesting TAp73 as a predictive marker for response to TGF-ß inhibitors, our study could improve the classification of PDA patients with a view to offering combined therapy involving TGF-ß inhibitors.

Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling.

Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of cancer, with few therapeutic options. Evidence supports an implication of the intratumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within the pathophysiology and clinical course of PDA, through tumor recurrence and neuropathic pain, remains unknown, neglecting a putative, therapeutic window. Here, we report that the intratumoral microenvironment is a mediator of PDA-associated neural remodeling (PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule), which is expressed by cancer-associated fibroblasts (CAFs), that impact on neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell migration/proliferation by modulating N-cadherin/ß-catenin signaling. Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural connection. Finally, we revealed that SLIT2 expression and CAFs are correlated with neural remodeling within human and mouse PDA. All together, our data demonstrate the implication of CAFs, through the secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of the stromal/neural compartment connection with SLIT2/ROBO inhibitors for the treatment of pancreatic cancer recurrence and pain.

TAp73 is required for macrophage-mediated innate immunity and the resolution of inflammatory responses.

The multiple isoforms of p73, a member of the p53 family, share the ability to modulate p53 activities but also have unique properties, leading to a complex and poorly understood functional network. In vivo, p73 isoforms have been implicated in tumor suppression (TAp73(-/-) mice), DNA damage (ΔNp73(-/-) mice) and development (p73(-/-) mice). In this study, we investigated whether TAp73 contributes to innate immunity and septic shock. In response to a lethal lipopolysaccharide (LPS) challenge, TAp73(-/-) mice showed higher blood levels of proinflammatory cytokines and greater mortality than their wild-type littermates. In vitro, TAp73(-/-) macrophages exhibited elevated production of tumor necrosis factor alpha , interleukin-6 and macrophage inflammatory protein-2 as well as prolonged survival, decreased phagocytosis and increased major histocompatibility complex class II expression. Mice depleted of endogenous macrophages and reconstituted with TAp73(-/-) macrophages showed increased sensitivity to LPS challenge. These results suggest that macrophage polarization is altered in the absence of TAp73 such that maintenance of the M1 effector phenotype is prolonged at the expense of the M2 phenotype, thus impairing resolution of the inflammatory response. Our data indicate that TAp73 has a role in macrophage polarization and innate immunity, enhancing the action field of this important regulatory molecule.

Acute aortic intramural hematoma presenting with painless recurrent syncope.

A patient presented with recurrent syncope due to transient severe hypotension. The patient's history, physical examination, and initial baseline investigation did not suggest a cardiovascular cause. After fluid resuscitation, a raised jugular venous pulse was noted. Bedside transthoracic echocardiogram showed a pericardial effusion and a proximally dilated aorta. Computed tomography of the thorax confirmed these findings and also demonstrated an intramural hematoma of the proximal aortic wall.The patient was transferred to a cardiothoracic center, where he was at first treated medically. He then developed sudden cardiogenic shock due to pericardial tamponade and was successfully operated on.It is important to recognize an acute intramural hematoma of the proximal aortic wall as a cardiothoracic emergency. This condition can present atypically, but nevertheless warrants urgent surgical intervention, equal to type A aortic dissection. Echocardiography can help in making the diagnosis.

Interlaboratory assessment of mitotic index by flow cytometry confirms superior reproducibility relative to microscopic scoring.

A flow cytometric procedure for determining mitotic index (MI) as part of the metaphase chromosome aberrations assay, developed and utilized routinely at Pfizer as part of their standard assay design, has been adopted successfully by Covance laboratories. This method, using antibodies against phosphorylated histone tails (H3PS10) and nucleic acid stain, has been evaluated by the two independent test sites and compared to manual scoring. Primary human lymphocytes were treated with cyclophosphamide, mitomycin C, benzo(a)pyrene, and etoposide at concentrations inducing dose-dependent cytotoxicity. Deming regression analysis indicates that the results generated via flow cytometry (FCM) were more consistent between sites than those generated via microscopy. Further analysis using the Bland-Altman modification of the Tukey mean difference method supports this finding, as the standard deviations (SDs) of differences in MI generated by FCM were less than half of those generated manually. Decreases in scoring variability owing to the objective nature of FCM, and the greater number of cells analyzed, make FCM a superior method for MI determination. In addition, the FCM method has proven to be transferable and easily integrated into standard genetic toxicology laboratory operations.

Short-term mortality and complications in ST elevation myocardial infarction--the Heart Hospital experience.

The mortality rate of acute myocardial infarction has declined considerably in the past three decades. In view of paucity of literature from different centres from India on this issue, the present study was undertaken to determine the in-hospital mortality with acute ST segment elevation myocardial infarction presenting to a tertiary care cardiac centre in India. Consecutive patients (n=862) with the diagnosis of acute ST segment elevation myocardial infarction admitted in Heart Hospital, Patna between June 2003 and July 2006 were included in this study. The in-hospital mortality and event rates (reinfarction, recurrent angina and heart failure) were analysed. The mean age of study population was 56 +/- 13 years. There were 690 males (80.05%) and 172 females (19.95%); 468 patients (54.29%) had hypertension, 384 patients (44.55%) were diabetic, 415 (48.14%) were smokers/tobacco chewers and 154 patients (17.86%) had past history of myocardial infarction. Anterior wall infarction was present in 435 patients (50.46%), 408 patients (47.33%) had inferior wall infarction, 115 patients (13.34%) had associated right ventricular or posterior wall infarction and 19 (2.20%) had antero-inferior infarction; 346 patients (40.14%) received thrombolytic therapy while the other patients were not thrombolysed due to various reasons (usually late arrival). The mean duration between symptom onset and hospital admission was 29.2. +/- 10.8 hours in the entire group (8.6 +/- 2.8 hours in the thrombolysed group). Of the total 862 patients, 107 patients (12.41%) died during in-hospital stay while 755 patients were discharged from the hospital in stable condition after a mean stay of 7.1 +/- 1.8 days. The in-hospital mortality rate of acute ST segment elevation myocardial infarction in this study was 12.41%, which is comparable to reports from the west. However the revascularisation rate (thrombolysis or PTCA) remained low and most patients received thrombolysis late.

Characterization of beta-turn and Asx-turns mimicry in a model peptide: stabilization via C--H . . . O interaction.

The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins.

Association of major modifiable risk factors among patients with coronary artery disease--a retrospective analysis.

BACKGROUND: The relative importance of various risk factors varies in different regions of India. This was a retrospective study of patients with recently diagnosed coronary artery disease to assess four major risk factors: dyslipidemia, hypertension, smoking and diabetes. MATERIAL AND METHODS: A total of 5748 patients (4952 males, 796 females) with recently diagnosed coronary artery disease were analysed from the records of Heart Hospital along with 8103 controls (6092 males and 2011 females). Absolute lipid levels as well as prevalence of dyslipidemia using the ATP III guidelines were assessed. They were classified into two major groups premature CAD (males < 45 years females < 55 years) and CAD at usual age (males > or = 45 years, females > or = 55 years). RESULTS: The most common pattern of CAD was chronic stable angina (n=2773, 48.24%). Mean total cholesterol (TC), LDL cholesterol and TC/HDL ratio were significantly higher in subjects with CAD compared to subjects without CAD controls. The mean HDL cholesterol and triglyceride levels were similar in both groups. Elevated LDL cholesterol, decreased HDL cholesterol, elevated total cholesterol and abnormal TC/HDL ratios were more common in CAD patients as compared to controls (38.8% vs. 33.14%, 29.3% vs 18.2%, 36.9% vs 32.5% and 59.05% vs 44.3% respectively). However lipid abnormalities were not significantly different in females > or = 55 in CAD vs non-CAD group. Smoking was significantly more common in subjects with CAD groups (30.97% vs. 12.72%) as compared to subjects without CAD (P < 0.0001). It was most common in males with premature CAD (44.1 % P < 0.0001). Hypertension was found in 1036 patients (18.02%) and diabetes in 763 (13.28%) as compared to 1126 (13.9%) hypertensives in non-CAD group and 639 diabetics (7.89%) (P = 0.001), both were more common in males > or = 45 and females > or = 55 as compared to those with premature CAD (p < 0.01). CONCLUSION: Among the risk factors assessed, dyslipidemia (particularly abnormal TC/HDL ratio and elevated LDL cholesterol), smoking hypertension and diabetes were associated with coronary artery disease in decreasing order of prevalence. In premature CAD, dyslipidemia and (in males) smoking are of particular importance.

Influence of hydrophobic interactions on the conformational adaptability of the beta-Ala residue.

The chemical synthesis and X-ray crystal structure analysis of a model peptide incorporating a conformationally flexible beta-Ala residue: Boc-beta-Ala-Pda, 1 (C23H46N2O3: molecular weight = 398.62) have been described. The peptide crystallized in the crystal system triclinic with space group P21: a = 5.116(3) A, b = 5.6770(10) A, c = 21.744(5) A; alpha = 87.45 degrees, beta = 86.87 degrees, gamma = 90.0 degrees; Z = 1. An attractive feature of the crystal molecular structure of 1 is the induction of a reasonably extended backbone conformation of the beta-Ala moiety, i.e. the torsion angles phi approximately -115 degrees, mu approximately 173 degrees and psi approximately 122 degrees, correspond to skew-, trans and skew+ conformation, respectively, by an unbranched hydrophobic alkyl chain, Pda, which prefers an all-anti orientation (theta1 approximately -153 degrees, theta2 approximately ellipsis theta14 approximately +/-178 degrees ). The observation is remarkable because, systematic conformational investigations of short linear beta-Ala peptides of the type Boc-beta-Ala-Xaa-OCH3 (Xaa = Aib or Acc6) have shown that the chemical and stereochemical characters of the neighboring moieties may be critical in dictating the overall folded and/or unfolded conformational features of the beta-Ala residue. The overall conformation of 1 is typical of a 'bar'. It appears convincing that, in addition to a number of hydrophobic contacts between the parallel arranged molecules, an array of conventional N-HellipsisO=C intermolecular H-bonding interactions stabilize the crystal molecular structure. Moreover, the resulting 14-membered pseudo-ring motif, generated by the amide-amide interactions between the adjacent molecules, is completely devoid of nonconventional C-HellipsisO interaction. The potentials of the conformational adaptation of the beta-Ala residue, to influence and stabilize different structural characteristics have been highlighted.

Genetic toxicity evaluation of octamethylcyclotetrasiloxane.

Octamethylcyclotetrasiloxane (OMCTS; CAS No. 556-67-2) was evaluated in a genetic toxicity battery. In preincubation tests with Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538, no mutagenicity was detected (maximum dose = 5 mg/plate) with or without S9 in two independent trials. Treatment of cultured Chinese hamster ovary (CHO) cells was limited by cytotoxicity at OMCTS concentrations greater than 0.003 mg/mL without S9 and 0.03 mg/mL with S9. CHO cells treated with up to 0.003 mg/mL without S9 and 0.03 mg/mL with S9 showed no significant dose-related increases in chromosomal aberration frequencies. No significant dose-related increases in sister chromatid exchanges (SCEs) occurred in OMCTS-treated CHO cells (maximum OMCTS concentration = 0.003 mg/mL without S9; 0.03 mg/mL with S9). Therefore, OMCTS was concluded to be negative in the SCE assay. In a screen for in vivo clastogenic potential, Sprague-Dawley rats received 700 ppm OMCTS by whole-body vapor inhalation 6 hr daily for 5 days. A negative control group received filtered air on the same schedule. A positive control group was exposed to filtered air on the same schedule and received cyclophosphamide 24 hr before termination. The OMCTS-treated animals were terminated 6 and 24 hr after the final exposure. Positive and negative control animals were terminated 24 hr after the last exposure. No significant, treatment-related increases in chromosomal aberrations were detected. The results of these studies indicate that OMCTS does not possess significant in vitro genotoxic potential. No adverse genetic findings were seen in the in vivo screen for chromosome aberrations.

Entrapping unusual folding characteristics of the beta-Ala residues in a model peptide: Boc-beta-Ala-Aib-beta-Ala-NHCH3.

Crystal structure analysis of a model peptide: Boc-beta-Ala-Aib-beta-Ala-NHCH3 (beta-Ala: 3-amino propionic acid; Aib: alpha-aminoisobutyric acid) revealed distinct conformational preferences for folded [phi approximately 136 degrees, mu approximately -62 degrees, psi approximately 100 degrees] and semifolded [phi approximately 83 degrees, mu approximately -177 degrees, psi approximately -117 degrees] structures of the N-and C-terminus beta-Ala residues, respectively. The overall folded conformation is stabilized by unusual Ni...H-Ni+1 and nonconventional C-H...O intramolecular hydrogen bonding interactions.

A study of lipid levels in uncomplicated hypertension.

A number of risk factors for coronary artery disease are known to be present in hypertensive patients, the most important being hyperlipidemia. An analysis of the lipid profiles of 3,182 uncomplicated non-diabetic patients (2,425 males, 757 females) who attended two institutions of Patna city between 1992-1998 was conducted alongwith 4,131 controls. Mean total cholesterol was slightly higher (but statistically significant; p < or = 0.05) in hypertensives (191.8 mg/dL vs 190.1 mg/dL) as compared to the control group; mean total cholesterol-HDL ratio was also higher (4.65 vs 4.48) in hypertensives (p < or = 0.05). As per National Cholesterol Education Programme guidelines, 1,069 (33.6%) patients had cholesterol level above 200 mg/dL while 850 (26.7%) had triglycerides over 200 mg/dL among the hypertensive group. An abnormal total cholesterol-HDL ratio (> 4.5) was found in 1,600 (50.3%) of the hypertensives; this was by far the most common abnormality. With increasing severity of hypertension, the prevalence of elevated total cholesterol, LDL cholesterol and low HDL cholesterol was higher; triglyceride levels were less affected. These results indicate that an abnormal total cholesterol-HDL ratio is the most common variety of dyslipidemia in uncomplicated hypertension.

Stabilization of a novel beta-turn-like motif by nonconventional intramolecular hydrogen-bonding interactions in a model peptide incorporating beta-alanine.

The chemical synthesis and x-ray crystal structure analysis of a model peptide incorporating a conformationally adaptable unsubstituted beta-Ala residue: Boc-beta-Ala-Acc6-OCH3 (C16H28N2O5, molecular weight = 328.41; 1) has been described. The peptide crystallized in the space group P2(1)2(1)2(1) a = 8.537 (3), b = 8.872 (10), c = 25.327 (8), alpha = beta = gamma = 90.0 degrees, Z = 4. An attractive feature of the crystal structure analysis of 1 is an accommodation of a significantly folded beta-Ala residue in a short linear peptide. The overall peptide conformation is typically folded into a beta-turn-like motif. The stabilization of the peptide backbone conformation by nonconventional C-H...O weak intramolecular hydrogen-bonding interactions, involving the ester terminal carbon atom and the ethereal oxygen of the Boc group, has been evoked. The conformational constraint that seems most apparent is the phi, psi value of the highly constrained hydrophobic Acc6 ring that may play a key role in inducing or sustaining the observed pseudo type III or III' beta-turn structure. The resulting 12-membered hydrogen bonding ring motif in 1 is distinctly different from the one found in classical beta-turn structures, stabilized by a conventional strong C=O...H-N intramolecular hydrogen bond, comprised of alpha-amino acids. The potential of the conformationally adaptable beta-Ala residue to occupy i + 1 position (left corner) of the folded beta-turn-like structure and to design and construct novel secondary structural features have been emphasized.