Lead as a Risk Factor for Osteoporosis in Post-menopausal Women.

Lead exposure is increasingly becoming an important risk factor for osteoporosis. In adults, approximately 80-90 % of absorbed lead is stored in the bones. These bone lead deposits are released into the blood during periods of enhanced bone resorption like menopause, forming a potential endogenous source of lead exposure. Postmenopausal women are at a higher risk for bone lead release because of hormonal and age related changes in bone metabolism. Estrogen deficiency is associated with increase in osteoclasts number and activity leading to both the early and late form of osteoporosis. Hence, high blood lead level coupled with concomitant environmental exposure exposes women in this age group to lead related adverse outcomes like hypertension, reduced kidney and neurocognitive functions as well as increased risk of atherosclerosis and cardiovascular mortality. A few studies have also identified coexisting variates like ethnicity, occupation, residence, education, smoking, alcohol medications, water etc. as significant determinants of bone and blood lead in women, thus increasing the magnitude of postmenopausal bone changes. Hence, interventions focused on reducing the intensity of bone resorption during menopause will help decrease exposure to endogenous lead. This would play a significant role in decreasing the morbidity and mortality associated with menopause. Also, identification of modifiable factors that prevent bone lead release will reduce the risk of chronic lead exposure and improve the health outcomes of post-menopausal women.

Lipoprotein (a): a Unique Independent Risk Factor for Coronary Artery Disease.

The current epidemic affecting Indians is coronary artery disease (CAD), and is currently one of the most common causes of mortality and morbidity in developed and developing countries. The higher rate of CAD in Indians, as compared to people of other ethnic origin, may indicate a possible genetic susceptibility. Hence, Lp(a), an independent genetic risk marker for atherosclerosis and cardiovascular disease assumes great importance. Lp(a), an atherogenic lipoprotein, contains a cholesterol rich LDL particle, one molecule of apolipoprotein B-100 and a unique protein, apolipoprotein (a) which distinguishes it from LDL. Apo(a) is highly polymorphic and an inverse relationship between Lp(a) concentration and apo(a) isoform size has been observed. This is genetically controlled suggesting a functional diversity among the apo(a) isoforms. The LPA gene codes for apo(a) whose genetic heterogeneity is due to variations in its number of kringles. The exact pathogenic mechanism of Lp(a) is still not completely elucidated, but the structural homology of Lp(a) with LDL and plasmin is possibly responsible for its acting as a link between atherosclerosis and thrombosis. Upper limits of normal Lp(a) levels have not been defined for the Indian population. A cut off limit of 20 mg/dL has been suggested while for the Caucasian population it is 30 mg/dL. Though a variety of assays are available for its measurement, standardization of the analytical method is highly complicated as a majority of the methods are affected by the heterogeneity in apo(a) size. No therapeutic drug selectively targets Lp(a) but recently, new modifiers of apo(a) synthesis are being considered.

Hyperhomocysteinemia, MMPs and Cochlear Function: A Short Review.

Hyperhomocysteinemia (HHCY) has been demonstrated to affect cochlear microvasculature as well as cochlear epithelial cells directly, with a resultant alteration of the expression of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Hence, ascertaining the optimum concentration of MMPs and TIMPs in the cochlea could help to inhibit hearing loss due to HHCY by the administration of appropriate MMP inhibitors, Since infections/inflammations as well as ototoxic antibiotics have a similar mechanism of otic pathology, the cochlear damage they cause could also be similarly prevented.

The potential of Cystatin C and small dense LDL as biomarkers of coronary artery disease risk in a young Indian population.

Coronary artery disease (CAD) affects Indians 5-6 years earlier than in the west, is diffuse and malignant, and poses a heavy burden on India's developing economy. Traditional risk factors have failed to explain this high incidence of premature CAD and hence this study investigated the association of two novel risk biomarkers, cystatin C and small dense LDL (sdLDL) with the presence and severity of CAD. Cystatin C and sdLDL were estimated in 204 CAD patients ≤45 years of age and compared with 161 age-matched healthy controls. The traditional lipid profile parameters, i.e., cholesterol, LDL, HDL, triglycerides, apolipoproteins A1 and B, and Lp(a) were also measured in both groups. Cystatin C was significantly raised and mean LDL particle size significantly reduced in CAD patients as compared to controls. 62.7 % of CAD patients showed pattern B while 37.3 % patients showed pattern A. Of the traditional lipid tests, only HDL and apolipoprotein A1 showed a significant decrease in the CAD group. sdLDL was significantly associated with the severity of CAD, while cystatin C was not. Both cystatin C and sdLDL emerged as independent risk factors, however, of the two, sdLDL was a more sensitive predictor of CAD events. Cystatin C and mean LDL particle size are significantly and independently associated with the presence of CAD events in patients ≤45 years with normal kidney function. Hence, these novel risk biomarkers can be useful tools in reducing the morbidity and mortality associated with CAD in the productive Indian workforce.

On the fine structure of the cambium of Fraxinus americana L.

The fine structure of ash cambium was studied after glutaraldehyde-osmium tetroxide fixation. The fusiform and ray initials are essentially alike, and both have the basic complement of organelles and membranes typical of parenchyma cells. The varied behavior of the two types of initials and the role of cambium in oriented production of the xylem and phloem are still unexplained phenomena. Actively growing cambial cells are highly vacuolate. They are rich in endoplasmic reticulum of the rough cisternal form, ribosomes, dictyosomes, and coated vesicles. Microtubules are present in the peripheral cytoplasm. The plasmalemma appears to be continuous with the endoplasmic reticulum and produces coated vesicles as well as micropinocytotic vesicles with smooth surfaces. The plastids have varying amounts of an intralamellar inclusion which may be a lipoprotein. The quiescent cambium is deficient in rough ER and coated vesicles and has certain structures which may be condensed proteins.

Healthcare biotechnology in India.

Biotechnology in India has made great progress in the development of infrastructure, manpower, research and development and manufacturing of biological reagents, biodiagnostics, biotherapeutics, therapeutic and, prophylactic vaccines and biodevices. Many of these indigenous biological reagents, biodiagnostics, therapeutic and prophylactic vaccines and biodevices have been commercialized. Commercially when biotechnology revenue has reached $25 billions in the U.S. alone in 2000 excluding the revenues of biotech companies that were acquired by pharmaceutical companies, India has yet to register a measurable success. The conservative nature and craze of the Indian Industry for marketing imported biotechnology products, lack of Government support, almost non-existing national healthcare system and lack of trained managers for marketing biological and new products seem to be the important factors responsible for poor economic development of biotechnology in India. With the liberalization of Indian economy, more and more imported biotechnology products will enter into the Indian market. The conditions of internal development of biotechnology are not likely to improve in the near future and it is destined to grow only very slowly. Even today biotechnology in India may be called to be in its infancy.

Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

BACKGROUND: In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. OBJECTIVE: The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. DESIGN: This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score <5 at 5 min, sepsis, cord blood not collected, or auditory evaluation unable to be performed. Sixty consecutive infants with risk factors for iron deficiency, such as small for gestational age and maternal diabetes, and 30 without risk factors for iron deficiency were enrolled. Absolute wave latencies and interpeak latencies, evaluated by auditory brainstem response within 48 h after birth, were measured and compared between infants with latent iron deficiency (serum ferritin ≤75 ng/mL) and infants with normal iron status (serum ferritin >75 ng/mL) at birth. RESULTS: Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P < 0.05). This difference remained significant on regression analyses after control for confounders. No difference was noted between latencies I and III and interpeak latencies I-III. CONCLUSION: Latent iron deficiency is associated with abnormal auditory neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397.

Increased disaccharidase activity in human diabetics.

Disaccharidase activity has been shown to be increased in human diabetics. Diabetics controlled on diet therapy showed no change in disaccharidase activity while two diabetics controlled on insulin or insulin-producing drug, glibenclamide, showed a fall in disaccharidase values toward normal. Possible causes for the increased disaccharidase activity in diabetes are discussed.

C3b receptor (CR1) genomic polymorphism in rheumatoid arthritis. Low receptor levels on erythrocytes are an acquired phenomenon.

The number of complement receptor 1 (CR1, CD35) molecules on erythrocytes is genetically determined by two codominant alleles. The numerical expression of CR1 on erythrocytes correlates with a HindIII-RFLP or CR1 gene using CR1-1, a complementary DNA probe. We have found low CR1 on erythrocytes in patients with rheumatoid arthritis (RA) in an Indian population. Low levels in RA patients may be acquired or genetically determined. Fifty-two patients with RA, 48 nonrelated healthy subjects and 19 consanguineous relatives of patients were genotyped. CR1 numbers on erythrocytes were quantitated by the enzyme-linked immunosorbent assay using monoclonal anti-CR1 antibody. Normal subjects and patients were followed up for a period of 6 months to evaluate the stability of their CR1 expression. The gene frequency for allele H and L (7.4- and 6.9-kb HindIII restriction fragment, respectively), which correlated with high and low expression of CR1 on erythrocytes was 0.77 and 0.23 in the normal controls. Gene frequency in RA patients was 0.78 and 0.22 for H and L allele, which did not differ significantly from either controls or relatives (0.80 and 0.20 for H and L allele, respectively). However, RA patients expressed fewer CR1 on erythrocytes within each genotype than their relatives and controls. CR1 on erythrocytes were found to be stable in consecutive samples in controls. In RA patients, the number varied between low and high during the course of the disease. The variation in number was significantly correlated (p < 0.05, r = -0.85 to -0.98) with disease activity as monitored by erythrocyte sedimentation rate. Our results suggest that low levels of CR1 on erythrocytes in patients with RA are not inherited, rather they are acquired during the course of the disease.

Lowered expression of C3b receptor (CR1) on erythrocytes of rheumatoid arthritis patients.

The number of C3b receptors (CR1) on erythrocytes (E) has been quantitated by whole cell enzyme-linked immunosorbent assay (ELISA), using a monoclonal anti-CR1 antibody, in 46 healthy individuals as controls, 58 having rheumatoid arthritis (RA) and 3 hereditary angioedema patients. The mean value of CR1 in RA (381/E) was significantly lower (p < 0.001) when compared to normal controls (646/E). In hereditary angioedema patients CR1 numbers (620/E) were found to be comparable to normal values. No significant difference was found between normal male (708/E) and female (598/E) subjects. Among the patient groups, those on steroid therapy (352/E) showed no change compared to others not receiving such therapy (408/E). The cumulative frequency curve of CR1 in the normal population showed maximum inflection at 32% and 82%. This led us to conclude that there is a trimodal distribution of receptors in the control population. Such a contention is well supported by frequency histogram, when a small group interval (0-50) was chosen. However, if large group intervals (0-100 or 0-150) were considered, a very close approximation to unimodal pattern was obtained. The factors actually contributing to low receptor numbers are yet to be elucidated.

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians.

BACKGROUND: A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. METHODS: DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. RESULTS: Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00-0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99-6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66-37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. CONCLUSIONS: Our study shows a significant association between rare S2 allele and HTG in Asian Indians.

Flow of couple stress fluid through stenotic blood vessels.

The effects of an axially symmetric mild stenosis on the flow of blood, when blood is represented by a couple stress fluid model, have been studied. It is found that, for a fixed stenosis size, the resistance to flow and wall shear stress increase as the couple stress parameter eta decreases from unity. A comparison of the results with those of the Newtonian case shows that the magnitude of resistance to flow and wall shear under a given set of conditions, is greater in the case of the couple stress fluid model. It is seen that even in the case of a mild stenosis (19% area reduction), resistance to flow and wall shear values are increased over those for no stenosis by 60% and 62%, respectively, when compared with the case of a Newtonian fluid.

Peristaltic transport of blood: Casson model--II.

The problem of peristaltic transport of blood in a uniform and non-uniform tube has been investigated, under zero Reynolds number and long wavelength approximation. Blood is represented by a two-layered fluid model consisting of a central layer of suspension of all erythrocytes, etc., assumed to be a Casson fluid, and a peripheral layer of plasma as a Newtonian fluid. A comparison of results with those without peripheral layer shows that the magnitude of the pressure rise, under a given set of conditions is smaller in the case of model with peripheral layer. It is found that, for a given flow rate, the pressure rise decreases as the viscosity of the peripheral layer decreases, and for a given non zero pressure drop, the flow rate increases as the viscosity of the peripheral layer decreases. However, the flow is independent of the presence of the peripheral layer, for zero pressure rise. Further, the pressure rise in the case of non-uniform geometry is found much smaller than the corresponding value in the uniform geometry.

Peristaltic transport of a two-layered model of physiological fluid.

The problem of peristaltic transport of a two-fluid (peripheral and core fluid) model in a non-uniform tube and channel has been investigated under long wavelength approximation. A comparison of these results with those for without peripheral layer fluid shows that the magnitude of the pressure rise under a given set of conditions is smaller in the case of with peripheral layer fluid. For a given non zero pressure drop, the flow rate increases as the viscosity of the peripheral layer fluid decrease. However, for zero pressure drop, the flow rate is independent of the presence of peripheral layer fluid. Pressure rise in the case of non-uniform geometry is found to be much smaller than the corresponding values in the case of uniform geometry. The analysis has been applied and compared with the observed flow rates of spermatic fluid (semen) in vas deferens of rhesus monkeys and to the experimental results of Weinberg et al. (1971).

Interaction of peristaltic flow with pulsatile flow in a circular cylindrical tube.

The effect of pulsatile flow on peristaltic transport in a circular cylindrical tube is analysed. The flow of a Newtonian viscous incompressible fluid in a flexible circular cylindrical tube on which an axisymmetric travelling sinusoidal wave is imposed, is considered. The initial flow in the tube is induced by an arbitrary periodic pressure gradient. A perturbation solution with amplitude ratio (wave amplitude/tube radius) as a parameter is obtained when the frequency of the travelling wave and that of the imposed pressure gradient are equal. The interaction effects of periodic wall induced flow and periodic pressure imposed flow are visualized through the presence of substantially different components of steady and higher harmonic oscillating flow in the first order flow solution. Numerical results show a strong variation of steady state velocity profiles with boundary wave number and Reynolds number and a strong phase shift behaviour of the flow in the radial direction.

Effect of alcohol on serum lipids & lipoproteins in male drinkers.

The evaluation of the effect of moderate and high doses of ethanol on the serum levels of triglyceride (TG), total cholesterol (TC), cholesterol content of very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), HDL2, HDL3 subfractions and apoproteins: apo-AI and apo-B was undertaken in 45 (25 controls, 10 moderate and 10 high dose drinkers) healthy males. The results of this preliminary study showed a significant rise in total HDL-cholesterol and apo-AI levels of alcoholics of both the groups. Out of the two subfractions, HDL2 appeared to be induced more. Increased levels of atherogenic lipids (TG, VLDL-chol., LDL-chol. and apo-B) were found in high as well as moderate drinkers. Our results suggest that the benefit of alcohol intake need to be weighed carefully against its considerable risks.

Effect of corticosteroid treatment on various serological & bronchoalveolar lavage abnormalities in patients with sarcoidosis.

Effect of daily oral prednisolone treatment was studied in 29 patients with pulmonary sarcoidosis. Twenty normal control subjects were also studied. Pretreatment absolute lymphocyte counts and proportion of lymphocytes in peripheral blood were significantly lower in patients with sarcoidosis as compared to normal controls. Total cell count and the proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid were significantly higher in sarcoidosis. The proportion of CD3+ and CD4+ was significantly lower in peripheral blood and higher in BAL fluid in patients with sarcoidosis. Immunoglobulins (IgG, A and M) and complements (C3, C4 and CH50) were significantly higher both in peripheral blood and BAL fluid. Patients with sarcoidosis were treated with daily oral prednisolone (30 mg/day). Repeat studies were performed after an interval of 4-6 months in 20 patients with sarcoidosis. A significant increase in absolute lymphocyte counts in peripheral blood and decrease in the proportion of lymphocytes in BAL fluid occurred with prednisolone treatment. Proportion of CD3+, CD4+ and B cells increased in peripheral blood and decreased in BAL fluid. Complement and immunoglobulin levels revealed a significant reduction in peripheral blood and BAL fluid. It is concluded that patients with sarcoidosis have peripheral blood lymphopaenia and lymphocytic alveolitis. They have increased levels of complement and immunoglobulins both in the peripheral blood and BAL fluid. All these abnormalities show significant improvement with prednisolone treatment.

On two-phase model of pulsatile blood flow with entrance effects.

A particle fluid suspension model is applied to the problem of pulsatile blood flow through a rigid circular tube with entrance effects. Flow is generated by an arbitrary (time and axial flow variable dependent) as well as a particular pressure gradient of physical importance. Fluid and particle phase velocities are explicitly determined for both, with and without entrance effects. Further, steady pulsatile velocities for both cases are deduced by taking time t -greater than . Several other limiting cases of physical and biological importance have been obtained and discussed in detail.

Peristaltic transport of a physiological fluid. Part-I. Flow in non-uniform geometry.

The problem of peristaltic transport of a fluid of variable viscosity in a non-uniform tube and channel has been investigated under zero Reynolds number, and long wavelength approximation. It is found that, the pressure rise decreases as the fluid viscosity decreases at zero flow rate, is independent of viscosity variation at a certain value of flow rate, and increases if flow rate exceeds further. The difference between two corresponding values (for constant and variable viscosity) of pressure rise, under a given set of conditions increases with increasing amplitude ratio at zero flow rate. Further, for a given zero pressure rise, the flow rate increases as viscosity of fluid decreases. The pressure rise, in the case of non-uniform geometry is found to be much smaller than the corresponding value in the case of uniform geometry. In Part II (a companion paper), results for uniform tube and channel are obtained and comparison with other theories are made in detail. Finally, the models developed in Part I and Part II are applied and compared with observed flow rates in vas deferens of rhesus monkeys, the small intestine, and the ductus deferens of the male reproductive tract in the other companion paper, Part III.

Peristaltic transport of a physiological fluid. Part - II. Flow in uniform geometry.

Using the model of peristaltic flow in non-uniform geometry, developed in the companion paper (Part I), results for uniform tube and channel are obtained in closed form. Comparison of analysis with other theories and the effect of viscosity variation are discussed in detail. Finally, quantitative comparison are made between theory and experiments of Weinberg et al. and Latham.