Impact of diet and physical activity on reproductive profile: A comparison of middle-aged and elderly men.

Age is a known determinant of reproductive health and fertility in both genders. The present work aims to assess the reproductive hormone profile of a middle-aged and elderly man. For this descriptive cross-sectional study, healthy male subjects (n=77) were recruited from the valley. Any individual suffering from any acute or chronic diseases and on drugs was ruled out from the study. Group A consisted of 40 elderly men between 60-70 years of age, and Group B comprised 37 men between 35-46 years of age. Blood samples were taken to estimate the reproductive hormone profile. Level of oxidant and antioxidant: Malondialdehyde and Glutathione. The demographic variables, which included retrospective and prospective questions, helped to assess the physical activity and diet intake behaviour of all inducted individuals. The analysis of the reproductive profile of both groups was similar and within the normal range of standards. However, the median level of LH was higher in group A than in group B: 6.7 mIU/ml versus 3.4 mIU/ml, respectively, and p<0.003. Both groups showed predominantly involvement in physical activity, >90%. The correlation of biochemical variables gives an insight into the fact that the Mediterranean diet and physical activity help to maintain a normal BMI. These implicate the normal secretion of various hormones, leading to intact spermatogenesis. We can safely deduce from this study that physically active lifestyles and a healthy diet are crucial factors in maintaining an endocrine profile.

L'âge est un déterminant connu de la santé reproductive et de la fécondité chez les deux sexes. Le présent travail vise à évaluer le profil hormonal de la reproduction d'un homme d'âge moyen et âgé. Pour cette étude transversale descriptive, des sujets masculins en bonne santé (n = 77) ont été recrutés dans la vallée. Toute personne souffrant de maladies aiguës ou chroniques et prenant des médicaments a été exclue de l'étude. Le groupe A était composé de 40 hommes âgés de 60 à 70 ans et le groupe B de 37 hommes âgés de 35 à 46 ans. Des échantillons de sang ont été prélevés pour estimer le profil des hormones reproductives. Niveau d'oxydant et d'antioxydant : Malondialdéhyde et Glutathion. Les variables démographiques, qui comprenaient des questions rétrospectives et prospectives, ont permis d'évaluer l'activité physique et le comportement alimentaire de tous les individus intronisés. L'analyse du profil reproducteur des deux groupes était similaire et se situait dans la fourchette normale des normes. Cependant, le taux médian de LH était plus élevé dans le groupe A que dans le groupe B : respectivement 6,7 mUI/ml versus 3,4 mUI/ml et p<0,003. Les deux groupes présentaient une participation prédominante à l'activité physique, > 90 %. La corrélation des variables biochimiques donne un aperçu du fait que le régime méditerranéen et l'activité physique contribuent à maintenir un IMC normal. Celles-ci impliquent la sécrétion normale de diverses hormones, conduisant à une spermatogenèse intacte. Nous pouvons déduire de cette étude qu'un mode de vie physiquement actif et une alimentation saine sont des facteurs cruciaux pour maintenir un profil endocrinien.

A Novel Link Between Adipokines And Lipoprotein (A) To Contemplate Their Diagnostic Role In Patients With Stemi And Nstemi.

BACKGROUND: Early detection of cardiac events allow better and cost-effective triage and welltimed management of these patients. Study was conducted to evaluate the prognostic significance of plasma adiponectin, resistin and lipoprotein (a) in a group of patients with ST segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. These parameters were also compared with other predictors like troponin T, troponin I and CK-MB. METHODS: Present study was based on the 100 patients with AMI of whom 52 had a diagnosis of STEMI, and 48 had NSTEMI. Duration of study was January to June 2015. Patients having chest pain that was indicative of myocardial ischemia within first 12 hours after the onset of symptoms were included in the study. Adiponectin, Lp (a), resistin, troponin T and troponin I were estimated using ELISA method. Level of CK-MB was measured by Auto-analyser using standard kit of Merck. RESULTS: Mean age of patients with STEMI was 52.32 years and with NSTEMI it was 48.17 years. Mean value of BMI of patients with STEMI was 28.33 and with NSTEMI was 25.22 Kg/m2. Duration of chest pain in patients with STEMI was 8.64 and patients with NSTEMI it was 16.52hours with highly significant difference (p<0.001). History of smoking in patients with STEMI was more as compared to the patients with NSTEMI. Level of CPK, adiponectin and lipoprotein (a) was raised in patients with STEMI as compared to patients with NSTEMI but significant difference was only found in levels of CPK (p<0.001) and in adiponectin (p<0.05). Level of serum CK-MB, TnT, TnI and resistin was raised in patients with NSTEMI as compared to patients with STEMI but significant difference (p<0.001) was only observed in serum troponin I concentration. CONCLUSIONS: It is concluded that the incidence of STEMI and NSTEMI is similar in our patients. However, the markers of STEMI are increased level of adiponectin and Lp(a) and the markers of NSTEMI are troponins especially troponin I, resistin and CKMB.

Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.

The protein kinase c-erbB-2 belongs to the family of receptor tyrosine kinase and is involved in oncogenesis. The present study predicts different phosphorylation sites of HER2/c-erbB-2 which are important in preventing or developing cancer, especially breast cancer. Sequence homology showed highest homology (77%) with epidermal growth factor receptor kinase domain. According to PROSITE search result, active sites of c-erbB-2 are N-lobe (glycine rich phosphate binding loop). Catalytic loop with presumptive catalytically active of Asp108 is phosphorylated by tyrosine protein kinase. A-loop, activation loop, becomes phosphorylated and activates the substrate binding. The study strengthens our knowledge regarding HER2 signaling by the detection of uncharacterized signaling proteins, establishing phosphorylation of an activation loop and helps us to make assumptions about the role of such previously unidentified proteins. On the basis of importance of HER2 in breast cancer as well as in other diseases, this study provides fruitful information for designing new therapeutic strategies.

CA 15-3 (Mucin-1) and physiological characteristics of breast cancer from Lahore, Pakistan.

BACKGROUND: High incidence of breast cancer and its fatal effect has reached an alarming stage across the globe, including the third world countries. Many factors have been reported to be associated with the development of breast cancer but detailed structural and functional information is missing. CA 15-3 is one of the known potential tumor marker of breast cancer; however little is known about structure and functional site of this protein. Present study aims to investigate the functional role of CA 15-3 in breast cancer, especially in development and metastasis. MATERIAL AND METHODS: Hundred female breast cancer patients confirmed by histopathological reports were included in the study. Their physiological characters were recorded in a performa. Enzyme linked immunosorbent assay (ELISA) technique was used to estimate serum CA 15-3 level. Immunohistochemistry was done for estrogen (ER), progesterone (PR) and Her2/neu receptors expression. RESULTS: The study revealed the details of physiological characteristics of female breast cancer. Mean age was 37.72 ± 5.99 and 55.05 ± 7.28 years and serum CA 15-3 (MUC1) level was 60.47 ± 8.59 and 63.17 ± 4.58 U/ml in pre and post-menopause respectively, and both groups of women had sedentary life style. Their receptor status especially of progesterone, estrogen and HER-2/neu were positive in 50% of premenopausal women and 65% of postmenopausal women. CONCLUSION: There are multiple physiological factors promoting breast cancer. High serum CA 15-3 level and hormonal imbalance of ER, PR and Her2/neu appears to be the main cause of breast cancer. It may be possible that the functional sites of these proteins may be altered which may increase the chances of metastasis in breast cancer.

Management of thrombocytopenia and flu-like symptoms in dengue patients with herbal water of Euphorbia hirta.

BACKGROUND: Incidence of dengue increased 30 fold between 1960 and 2010. This increase is believed to be due to a combination of urbanisation, population growth, increased international travel, and global warming. We tried to find out the effect of herbal water of Tawa-tawa, also called Euphorbia hirta, on the flu like symptoms and blood parameters especially on thrombocytopenia. METHODS: Total 125 patients with confirmed dengue fever admitted in medical ward of Sir Ganga Ram Hospital Lahore were included in this experimental study. Duration of study was 3 months. Patients were divided into 2 groups, i.e., group A (ages between 30 to 55 years) and group B (ages between 14 to 25 years). A blood sample was obtained on the day of enrolment and after 24 hours of using Tawa-tawa. The variables used were platelet count, haematocrit (HCT), WBC count, serum AST, ALT, IgM/IgG. RESULTS: In men, platelet count was < 25,000 and in women, it was > 50,000. Haematocrit were >40% in men and 30-40% in women. TLC in a range of 4,000-11,000/mm3 was observed in both males and females. IgM 'haemagglutination' antibody titres (> 1:160) was observed in 71.3% females and 50% males. Serum AST was > 40 IU/L in 38% females and 36% males. Serum ALT was > 40 IU/L in 9.5% females and 12% males. In both group A and B platelet count and TLC were increased nonsignificantly after herbal water of Euphorbia hirta (E. Hirta). Haematocrit value decreased nonsignificantly after using the herbal water. Over 70% of patients showed moderate increase in their platelet count. However leucopoenia improved significantly after the use of aqueous extract of E. hirta. A marked recovery in fever and flu like symptoms was observed. CONCLUSION: In over 70% patients there was improvement in platelet count, TLC, fever, and flue-like symptoms.

Serum trace elements in diagnosis of breast malignancy.

BACKGROUND: Breast cancer is a highly heterogeneous disease globally. The absolute risk of breast cancer increases with age and is higher in postmenopausal women. This study tried to find out role of serum trace elements (cadmium, cobalt, copper and zinc) and biomarkers in diagnosis of breast malignancy. METHODS: Levels of serum trace elements were estimated by atomic absorption spectrophotometry in serum samples of 23 breast cancer patients of stage III. Analysis of protein pattern was observed by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: In menstruating women, the mean serum level of cadmium, copper and cobalt were significantly lowered as compared to control, however, zinc showed no significant difference. In premenopausal and postmenopausal women, the mean serum level of cadmium, copper, cobalt and zinc was decreased significantly in patients as compared to controls (p < 0.001). The ratio of Cu/Zn was also decreased in patients when compared to controls. Three major peptide bands with molecular weights of 33 kDa, 52 kDa and 185 kDa appeared in these samples when subjected to SDS PAGE. CONCLUSIONS: Serum trace elements are significantly lower in breast cancer patients compared to controls. The exact mechanism responsible for the alterations in trace element levels in patients with breast cancer is unclear and requires further evaluation. Gel electrophoresis may be important to find out breast cancer markers that may help in diagnosing the disease and response to treatment.

Screening of pneumococcal pneumonia by amplification of pneumolysin gene in children visiting hospitals in lahore, pakistan.

OBJECTIVE: Streptococcus pneumoniae is a common worldwide potential pathogen causing pneumonia among children and the detection of pneumococcal infections by conventional culturing techniques is cumbersome. The present study describes a comparative analysis of sensitive nested-PCR and bacterial culture in pediatric patients with clinical and radiological indication of S. pneumoniae infection. METHODS: PCR was performed using outer primers to amplify a 348-bp region and inner primers a 208-bp region of the pneumolysin gene. For pneumolysin PCR assay, DNA from peripheral blood and middle ear fluid (MEF) samples was extracted by salting out method. The sensitivity of the assay was evaluated with about 0.06 pg of purified S. pneumoniae genomic DNA. FINDINGS: Among 90 MEF culture negative samples from acute otitis media pediatric patients, 8.8% pneumolysin-PCR positivity was detected, demonstrating the sensitivity and reliability of PCR for rapid pneumonia evaluation. Binomial test of proportionality performed on (SPSS 17) gives P< 0.05 indicating that PCR technique is statistically significant and sensitive in the diagnosis of S. pneumoniae infection. CONCLUSION: The research work evaluated the effectiveness and efficacy of nested-PCR for detecting S. pneumoniae in pediatric patients with clinical and radiological confirmation of bacterial infection. This simplified method permitted quick selection of the patients and played a significant role in preliminary management of pneumococcal infections.

Granzyme M: characterization with sites of post-translational modification and specific sites of interaction with substrates and inhibitors.

Granzymes kill cells in a variety of ways. They induce mitochondrial dysfunction through caspase dependent and caspase-independent pathways and destroy DNA and the integrity of the nucleus. For gaining a better understanding of the molecular function of granzyme M and its NK cell specificity, structural characterization of this enzyme by molecular modeling as well as its detailed comparison with other granzymes is presented in this study. The study includes mode of action of granzyme M using cationic binding sites, substrate specificity, post-translational structural modification and its functional relationship and interaction of the enzyme with inhibitor in an attempt to explore how the activity of human granzyme M is controlled under physiological conditions. It is concluded from the present study that the post-translational modification, including Oglycosylation of serine, phosphorylation of serine and threonine and myristoylation of glycine, play an important role in the interaction of enzyme with the cell surface membrane and regulate protein trafficking and stability. Phosphorylated serine and threonine also plays a role in tumor elimination, viral clearance and tissue repair. In Gzm M there are cationic sites, cs1 and cs2 that may participate in binding of Gzm M to the cell surface, thereby promoting its uptake and eventual release into the cytoplasm. Gzm M shows apoptotic activity both by caspase dependent and independent pathways. Modeling of inhibitors bound to the granzyme active site shows that the dimer also contributes to substrate specificity in a unique manner by extending the active-site cleft.

Role of phytoestrogen in suppressing bone turnover in a group of postmenopausal women.

BACKGROUND: Osteoporosis has emerged a major health hazard in postmenopausal women. The process of osteoporosis accelerates two year prior to menopause, reaching the peak level during first 3 years of menopause when women loss 3 (see symbol) 5% of their bone mass per year. This study tried to find out the role of phytoestrogne in improving the bone mineral density and bone related biochemical parameters in group of postmenopausal women. METHODS: Fifty postmenopausal women with age range 50 (see symbol) 60 years were included in the study. Phytoestrogen with mineral supplement were given twice daily for 3 months. Biochemical parameters like serum calcium, magnesium, alkaline phosphatase, uric acid, total protein and oestrogen were determined before and after phytoestrogen therapy by autoanalyser and ELIZA (oestrogen assay). T-score before and after phytoestrogen were find out by densitometer DEXA. RESULTS: The level of serum calcium, magnesium, uric acid and oestrogen was increased in women after taking phytoestrogen but significant difference (p < 0.01) was only observed in case of serum calcium. Level of serum alkaline phosphatase and total serum protein were slightly increased with no significant different before and after phytoestrogen therapy. Value of T-score was although markedly decreased after phytoestrogen therapy but it showed no significant difference. CONCLUSION: It is concluded that as the early years of menopause are a period of rapid bone loss, and the risk for osteoporosis increases substantially, the habitual intake of soy protein and isoflavones may play a role in the retardation of bone loss.

Alpha-1 microglobulin: a marker for early detection of tubular disorders in diabetic nephropathy.

BACKGROUND: Tubular damage as suggested by tubular proteinuria is a recognised feature of glomerulonephritis. The objectives of the study were to compare the level of alpha-microglobulin in normal and diabetic patients, and also to find out whether the level of alpha-1 microglobulin could become a laboratory marker for tubulo-interstitial damage in diabetic nephropathy. METHODS: Twenty-nine registered Type II diabetic patients of either sex were studied. The patients' age ranged from 41-50 years who were admitted in the medical ward, and those who visited the outdoor department of Sir Ganga Ram Hospital, Lahore were included in the study. The duration of study was one year from June 2006 to June 2007. Ten normal subjects with no history of diabetes were taken as controls. Blood samples and 24 hour urine samples of patients of all groups were collected. The levels of urinary protein and blood sugar were estimated by auto analyser. Proteinuria positive urinary samples were analysed by SDS-PAGE electrophoresis. RESULTS: The level of alpha-1 urinary protein was significantly increased in the group of diabetic patients as compared to the urinary protein level of normal subjects. Blood sugar level was also significantly increased in patients as compared to controls. Level of low molecular weight protein alpha-1 microglobulin showed an electrophoresis band of 28 Kda with an average volume of 6741.88 in the urine sample of patients. On the other hand, a very light, hardly recognisable band was observed in normal subjects. CONCLUSION: Urinary alpha-1 microglobulin provides a noninvasive and inexpensive diagnostic alternative for the diagnosis and monitoring of urinary tract disorders, i.e., early detection of tubular disorders of diabetic nephropathy. We propose that SDS-PAGE electrophoresis is a comparatively inexpensive diagnostic approach to detect this marker in the urine sample.

Diagnostic significance of adenosine deaminase in pleural tuberculosis.

BACKGROUND: Tuberculosis (TB) is a major cause of pleural effusion, which in TB usually has lymphocytic and exudative characteristics. Analysis of adenosine deaminase (ADA) activity is a very useful diagnostic approach to achieve a more rapid and precise diagnosis in cases of Pleural TB (pTB). METHODS: Fifty male and fifty female patients presenting with tuberculous pleural effusion was included in the study. The patients were taken from the medical ward of Sir Ganga Ram Hospital between September 2001 and September 2002. Activity of Adenosine Deaminase (ADA) was estimated by the technique of Sodium dodecyl sulphate electrophoresis (SDS-EF) using 10% polyacrylamide gel. RESULTS: Mean age of males was 45.72 +/- 19.22 years and of female was 43.74 +/- 16.09 years. Mean protein level was 3.39 +/- 0.24 g/dl in males, and it was 3.02 +/- 0.26 g/dl in females. Mean specific gravity both in males and females was 1.020 +/- 0.01. The results show an increased level of enzyme ADA in patients as compared to normal subjects. CONCLUSION: Estimation of ADA activity may provide basis for rapid and efficient diagnosis of pleural TB in different clinical settings. However study should be extended to larger number of patients to reach a better conclusion.

Bone mass measurement and factors associated with risk of fracture in a group of peri- and postmenoupausal women.

BACKGROUND: This study tried to find out the physiological risk factors as well as biochemical factors in a group of Pakistani peri- and postmenopausal women. MATERIALS AND METHOD: One hundred female subjects with age range of 40-52 years were included in the study. Female subjects were divided into two groups, i.e., 65 women with perimenopausal status age range 40-52 years old and 35 women with post menopausal status age range of 50-60 years. Detailed histories of subjects including factors that may contribute in bone fracture were recorded. Bone density was scanned. Blood parameters like serum calcium, alkaline phosphatase, total protein and uric acid were estimated. RESULTS: It was found that 70% of perimenopausal women belonging to class B were physically active. Hormonal replacement therapy (HRT) was observed in 25-30% of both groups. On the other, only 15% of both groups used oral contraceptives. Family history was found to be only in 10% of both groups. Level of serum calcium of perimenopausal/postmenopausal was less than normal control subject. Although the level of alkaline phosphatase was increased in perimenopausal women as compared to postmenopausal women and normal control subjects. Bone density of both peri- and postmenopausal women significantly decreased as compared to T score of normal control. CONCLUSION: It was concluded that a number of factors are predictive of future risk for the development of osteoporosis in women of reproductive age. Given the severity of the medical consequences of osteoporosis, the medical community needs to assess all women for these risk factors during their perimenopausal years.

To study the significance of apoptotic enzyme granzyme H in breast cancer patients.

BACKGROUND: Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. The rising global incidence, morbidity and mortality from breast cancer have led to intensified efforts in search for etiological factors of the disease. Present study tried to find out the significance of apoptotic enzyme granzyme H in breast cancer patients. METHODS: It was a cross sectional study. Fifty women with pre/post menopausal status were included in the study. Their physiological characteristics including age at menarche, menopause, life style and receptor status including oestrogen, progesterone and HER 2-neu were recorded. Level of serum granzyme H was estimated. RESULTS: It was observed that there is a variation in physiological characteristics. Level of serum granzyme was increased in patients before chemotherapy that may be decreased after treatment but not as much decreased as in normal control subjects. CONCLUSION: Increased level of granzyme H after chemotherapy may indicate the response of treatment. A direct relationship of oestrogen with granzyme H was also observed. However further study is suggested to reach a better conclusion.

MUC1 based breast cancer vaccines: role of post translational modifications.

BACKGROUND: Vaccine development is one of the most promising fields in cancer research. After autologous transplantation, due to low tumour burden, patients are more likely to respond immunologically to a cancer vaccine. MUC1 with its adhesive and antiadhesive functions, immunostimulatory and immunosuppressive activities, is therefore a good candidate for breast cancer vaccine. A structure-based insight into the immunogenicity of natural MUC1 glycoforms, of its sub-domains, motifs and post translational modification like glycosylation and myriostoylation may aid the design of tumour vaccines. METHODS: Primary sequences of human MUC1 were retrieved from the SWISSPROT data bank. Protein pattern search: The primary sequence of Human MUC1 was searched at PROSITE (a dictionary of protein sites and patterns) database. RESULTS: Our study observes that post-translational modifications play an important role in presenting MUC1 as a candidate for breast cancer vaccine. CONCLUSION: It is found that the phosphrylation and glycosylation of important functional motifs of MUC1 may take part in the production of cytokines that may provide immunization.

Three-dimensional structure prediction of bovine AP lyase, BAP1: prediction of interaction with DNA and alterations as a result of Arg176-->Ala, Asp282-->Ala, and His308-->Asn mutations.

BAP1 is an apurinic/apyrimidinic lyase (AP lyase) that plays an important role in the repair of DNA damage. The present study deals with the prediction of the 3D structure of bovine AP lyase based on its sequence homology with human AP lyase. The predicted 3D model of bovine AP1 shows remarkable similarity with human endonuclease in the overall 3D fold. However, significant differences in the model and the X-ray structure were located at some of the important sites. We have analyzed the active center of the enzyme and other sites that are involved in DNA repair. A number of amino acids bind the bases located in the major/minor grooves of DNA. An insertion of Arg176 in the major groove and Met270 in the minor groove caps the DNA bound enzyme's active site, stabilizing the extra helical AP site conformation and effectively locking the protein onto the AP-DNA. Three BAP1 mutants were also modeled and analyzed as regards the changes in the structure. Substitution of Arg176-->Ala leads to the loss of DNA binding whereas mutation of Asp282-->Ala and His308-->Asn leads to a decrease in the enzymatic activity.

Modeling the mutational effects on calmodulin structure: prediction of alteration in the amino acid interactions.

Calmodulin (CaM) is a highly conserved 17kDa eukaryotic protein that can bind specifically to over 100 protein targets in response to a Ca2+ signal. Present study was planned to mutate the crucial residues of N-terminal lobe, central helix, and C-terminal lobe that play important roles in activating and binding of enzymes. In all, 10 mutations were carried out in the predicted 3D structure of calmodulin using the computer program MODELLER 6v2. Mutations at specific residues in both the N-terminal and C-terminal regions resulted in the change in the interaction pattern of these amino acids. No significant change was however predicted by mutating amino acid residues in the central helix. The predicted alteration in the interaction of specific amino acids may either alter the binding affinity with calcium ions or decrease the ability of calmodulin to activate the specific enzymes.

Sensitivity and resistance of antibiotics in common infection of male and female.

BACKGROUND: There is increasing concern regarding antimicrobial resistance in Pakistan. Data are limited on the prevalence, pattern of resistance and risk factors associated with resistant organisms. This Study was done to address these issues as they relate to common infection of male/female. METHODS: Different clinical materials collected from 100 patients admitted in hospital or who attended out door clinic were used. Antibiotics like Enoxabid, Fortum, Ceporex, Klaricid, Maxaquin, Zenacef, Ceporexin, Urixin, Septran, Keflex. Erythrocine, vibramycin and tetracycline were used for culture sensitivity. RESULTS: It was observed that most of the pus specimens received are from females and urine specimens from males. Specimen of pus contains mostly Staph aureus, Urine specimen contain mostly E. coli whereas Pseudomonas pyrogenosa and proteases were also observed in urine, pus, sputum and ascitic/pleural fluids of patients. Among all drugs that were used, Enoxabid, Ceporex were vary sensitive against strains of Staph and Pseudomonas present in specimen. Strains of proteases were resistant against these drugs. Urixin and Septran show mixed action. In comparison of Enoxabid, Ceporex and Ceporexin, Zenocef and Fortum show sensitivity in fewer cases of Staph and E. coli. Mexaquin shows a good sensitivity against Pseudomonas and E. coli. It was observed that Septran, Erythrocine, Vibramycin, Tetracycline, Klaracid and Keflex are not very good acting drugs in infection of urine, pus, sputum and fluids. Finding of a low but definite level of resistance to septran, erythrocine, Vibramycin, Tetracycline, Klaracid and Keflex is important for selection of empiric therapy for infection.