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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 19 recordsLinked to original sources
PubMed2003

Particle size of liposomes influences dermal delivery of substances into skin.

In the present study, the influence of vesicle size on the penetration of two fluorescently labeled substances into the human skin was investigated. For the measurements either a hydrophilic fluorescent compound [carboxyfluorescein (CF)] or a lipophilic one [1,1'-dioctadecyl-3,3,3',3'-tertramethylindocarbo-cyanine perchlorate (DiI)] were encapsulated into vesicles. Liposomal formulations were prepared by extruding the vesicles through polycarbonate membrane filters with pores of different sizes. In vitro penetration studies into human abdominal skin were performed by using the Franz diffusion cell and a standardized skin stripping technique in attempt to find an optimum size for topical drug delivery by liposomes. Confocal laser scanning microscopy (CLSM) was used to visualize the effect of penetration ability of liposomal DiI. The maximum DiI fluorescence in the skin was observed with smaller liposomes of 71 nm diameter. The liposomes with a size of 120 nm diameter showed statistically enhanced penetration of CF into the skin as compared to larger ones. The results indicated that the CF penetration was inversely related to the size of the liposomes, which was confirmed by the data of the confocal laser scanning microscopy studies.

Administration, Topical↗
PubMed2003

Liposomes increase skin penetration of entrapped and non-entrapped hydrophilic substances into human skin: a skin penetration and confocal laser scanning microscopy study.

Liposomes have been extensively studied and suggested as a vehicle for topical drug delivery systems. However, the mechanism by which liposomes deliver drugs into intact skin is not fully understood. In the present study, we have tried to understand the mechanism of transport of hydrophilic drugs into the skin using liposomes. The effect of separation of the non-entrapped, hydrophilic fluorescent compound, carboxyfluorescein (CF), from liposomally entrapped CF was investigated by measuring the penetration of CF across human skin under non-occlusive conditions in vitro using Franz diffusion cells. The fluorescent dye, CF, was incorporated into the liposomes and applied onto the skin. After a 6 and 12h incubation period, the amount of CF in the epidermal membrane and the full thickness skin was determined by fluorescence spectroscopy or by confocal laser scanning microscopy (CLSM). The liposomal formulation containing CF both inside and outside the vesicles showed statistically enhanced penetration of CF into the human stratum corneum (SC) as compared to the formulations containing CF only outside of the liposomes and CF in Tris buffer. The CLSM results revealed that the formulation in which CF was present outside the liposomes showed bright fluorescence intensity in the SC and very weak fluorescence in the viable epidermis. However, the CF in Tris buffer failed to show any fluorescence in the viable epidermis. The results indicated that phospholipid vesicles not only carry the entrapped hydrophilic substance, but also the non-entrapped hydrophilic substance into the SC and possibly into the deeper layers of the skin.

Diffusion Chambers, Culture↗
PubMed2002

[Oral and extraoral disease due to betel nut chewing].

BACKGROUND AND OBJECTIVE: Betel chewing is common in India and southeast Asia. It shows mild psychostimulatory effects but with prolonged use there is a risk of oral and extraoral disease. Surprisingly, betel nut associated disorders are rarely discussed in the dermatological literature. METHODS: A review about betel nut associated disease is given based on a literature review and our own experiences. RESULTS: Both benign and malignant diseases can be induced by betel nut chewing. Betel causes reddish discoloration of teeth, periodontitis and buccal mucositis. Submucous fibrosis is a precancerous disease that may eventually develop into oral squamous cell cancer (OSCC). Among malignant diseases induced by betel quid, OSCC is the most important but esophageal cancer and hepatocellular cancer can also be observed. The available treatments are of limited value. CONCLUSIONS: Betel nut chewing has its own morbidity and mortality due to the induction of benign and malignant diseases. There is a lack of controlled trials although both betel nut chewing and the associated diseases are common.

Areca↗
PubMed2002

Helicobacter pylori eradication ameliorates symptoms and improves quality of life in patients on long-term acid suppression. A large prospective study in primary care.

Our objective was to determine prescribing patterns for H2 receptor antagonists (H2RA) in primary care and to establish the prevalence and impact of Helicobacter pylori (Hp) eradication in this population of patients. Patients on long-term (6 months or longer) H2RA were identified through a computerized database at the six primary care practices in North England. Hp status was identified by serology, and those positive received standard proton pump-based triple therapy followed by a urea breath test to confirm Hp eradication. The main outcome measures were the indications for prescribing long-term H2RA in primary care, the prevalence of patients with a positive Hp serology, and the impact of Hp eradication on the subsequent need for acid suppression, severity of dyspepsia, gastrointestinal symptom rating score (GSRS), quality of life (QOL), and overall feeling of well-being. One thousand seven (1.5%) patients were on long-term H2RA. Peptic ulcer disease (PUD) was the most common indication for prescribing (42%), followed by nonulcer dyspepsia (28%) and gastroesophageal reflux disease (23%). In 81% of the patients treatment with H2RA therapy followed a previous endoscopic or radiological investigation. Only 27 (2.5%) patients had had their Hp status checked within the last 6 months. Of the 471 patients who eventually had their Hp serology tested, 297 (63%) were Hp positive. Fifty-eight percent of the Hp-positive patients had PUD. Successful Hp eradication was achieved in 250 (84%) of the patients, of whom 247 (83%) finished the 1-year follow-up. This was associated with a significant reduction in the amount of H2RA being consumed (P < 0.00001). There was also a significant improvement in the symptom scores and the GSRS after successful Hp eradication (P < 0.00001). Overall 67% of the patients reported an improvement in the QOL and 77% noted a feeling of well-being 1 year after Hp eradication. A significant proportion of patients in primary care is still being maintained on long-term H2RA, imposing a considerable financial drain on the NHS resources. Approximately two-thirds of these patients will be Hp positive, and among them the largest group will comprise patients with PUD. Hp eradication in such patients results in a significant reduction in usage of acid suppression and an improvement in overall QOL and severity of dyspeptic symptoms.

Anti-Ulcer Agents↗
PubMed2002

Effect of annular incision type on the change in biomechanical properties in a herniated lumbar intervertebral disc.

The technique used to incise the disc during discectomy may play a role in the subsequent healing and change in biomechanical stiffness of the disc. Several techniques of lumbar disc annulotomy have been described in clinical reports. The purpose of this paper was to study the influence of annulotomy technique on motion segment stiffness using a finite element model. Four incision methods (square, circular, cross, and slit) were compared. The analyses showed that each of the annular incisions produced increase in motions under axial moment loadings with circular incision producing the largest change in the corresponding rotational motion. Under shear loading mode, cross and slit-type annular incisions produced slightly larger changes in the principal motions of the disc than square and circular incisions. All other incision types considered in the current study produced negligibly small increase in motion under rest of the loading conditions. In addition to annulotomy, when nucleotomy was also included in the analyses, once again cross and slit incisions produced larger change in motion under shear loading mode as compared to the other two incision types. A comparison between the four types of annular incisions showed that cross incision produced an increase in motion larger than those produced by the other three incisions under flexion/extension and lateral moment loading and both shear force loadings. Circular incision produced the largest increase in motion under axial moment load in comparison to those produced by square, cross, and slit incisions. Sagittal plane symmetry was influenced by the incision injury to the motion segment leading to coupled motions as well as increased facet loads. From the study it can be concluded that the increase inflexibility of the disc due to annulotomy depends on the type of annulotomy and the annulotomy also produce asymmetrical deformations leading to increased facet loading.

Computer Simulation↗
PubMed2002

Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis.

AIMS: Preliminary studies have suggested that there is an increase in adipocytic tissue in osteoporotic (OP) bone, supporting in vitro evidence for a switch in differentiation of stromal cells from the osteoblastic to the adipocytic lineage. To investigate this the variation of the ratio of adipose tissue to haemopoietic/stromal tissue in OP bone was measured. METHODS: The ratio of adipocytic to haemopoietic/stromal tissue (A/H) was measured by semi-automated image analysis in iliac crest biopsies from 127 patients with osteoporosis (84 female patients, 48 male patients; mean age, 55 years; range, 5-80). Fourteen patients with normal histomorphometric data (nine women; five men; mean age, 48 years; range 21-70) acted as controls. RESULTS: The ratio of A/H was higher in OP bone than in the normal controls (OP mean 43.06% v normal mean 22.4%; p < 0.001). Multiple regression analysis showed that 98.5% of the variability in the A/H ratio was the result of age and several measures of bone formation, including cancellous wall thickness, osteoid volume, cancellous thickness, cortical wall thickness, cancellous apposition rate, and bone formation rate, together with cancellous separation (each significant at p < 0.001). Those with the greatest effect on the A/H ratio (in decreasing order) were cancellous apposition rate, osteoid volume, and age. CONCLUSIONS: Cancellous apposition rate, osteoid volume, and age were associated with the increase in the proportion of adipose tissue present in OP bone. Of these, cancellous apposition rate reflects osteoblast activity, indicating that the increase in the volume of adipose tissue in osteoporosis is associated with reduced bone formation, supporting the postulated switch in differentiation of stromal cells from the osteoblastic to the adipocytic pathway in osteoporosis.

Adipocytes↗
PubMed2001

Cyclooxygenase-2 blockade does not impair endothelial vasodilator function in healthy volunteers: randomized evaluation of rofecoxib versus naproxen on endothelium-dependent vasodilatation.

BACKGROUND: From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has been a topic of increasing concern. This concern stemmed from observations indicating that the COX-2 isoform is the major source of endothelium-derived prostacyclin and, hence, that selective blockade of this enzyme may impair endothelial health. To investigate this matter, we examined the effects of 7 days of treatment with rofecoxib versus naproxen on endothelial function in healthy volunteers. METHODS AND RESULTS: Thirty-five healthy volunteers were randomized to receive 7-day treatment with either rofecoxib (25 mg/d, n=18) or naproxen (750 mg/d, n=17). Vascular response measurements were conducted using forearm strain-gauge plethysmography. Changes in forearm blood flow in response to the endothelium-dependent vasodilator acetylcholine (3, 10, and 30 microg/min) and the endothelium-independent vasodilator sodium nitroprusside (1 and 10 microg/min) were assessed before and after treatment. Acetylcholine evoked a dose-dependent increase in forearm blood flow in all groups. Importantly, treatment resulted in no change in acetylcholine-mediated increases in forearm blood flow in either group (naproxen, P=0.27; rofecoxib, P=0.58). Similarly, there was no change in forearm blood flow in response to sodium nitroprusside (naproxen, P=0.55; rofecoxib, P=0.63). CONCLUSIONS: We herein describe, for the first time, the effects of COX-2-selective inhibition on endothelium-dependent vasodilatation in healthy adults. COX-2 blockade, when used at the doses employed therapeutically (which are known to inhibit vascular prostacyclin production) did not result in significant changes in endothelial vasodilator responses in healthy volunteers. The effects of COX-2 inhibitors on vasodilator responses in patients with coronary artery disease remain to be determined.

Acetylcholine↗
PubMed2001

Tolerability and effectiveness of atypical antipsychotics in male geriatric inpatients.

The atypical antipsychotics are gradually becoming the mainstay of treatment for psychosis in the elderly. The present study examines the effectiveness and tolerability of risperidone and olanzapine treatment in 34 matched male patients admitted to a VA Medical Center geriatric inpatient unit. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Cohen-Mansfield Agitation Inventory (CMAI), the Rating Scale for Side-Effects, the Extra-Pyramidal Rating Scale, and the Mini-Mental State Examination were administered at admission and discharge. T-tests at admission and discharge across groups indicate that the patients as a whole were performing significantly better following their stay on the CMAI (t(30)=4.31, p=0.000), the GAF (t(31)=9.73, p=0.000), the PANSS total score (t(29)=3.82, p=0.001), and the positive symptom portion of the PANSS (t(28)=4.29, p=0.000). No significant differences were detected between the two groups with regard to length of hospitalization, or reduction in scores on the PANSS, or CMAI, however the daily cost of risperidone was 1/3 as much as olanzapine (p=0.00). The two treatments were comparable in the elderly men evaluated in this study.

Aged↗
PubMed2001

Nucleobase-containing metallated polymeric resins as artificial phosphodiesterases: kinetics of hydrolysis, pH dependence, and catalyst recycling.

Two metallated polymeric resins that contain the nucleobase adenine have been investigated for their ability to catalyze the hydrolysis of model phosphodiester substrates. These resins behave in a catalytic manner and display classical Michaelis-Menten kinetics. Consequently, parameters such as kobs, Km, Vmax, and kcat were determined for the two resins for both of the substrates. The most attractive feature of our nucleolytic system is its facile reusability that permits catalysis of multiple hydrolytic reactions, after resin recovery and a simple washing step, without significantly compromising the reaction rate. Involvement of a hydrolytic mechanism for phosphodiester cleavage is proposed on the basis of pH versus hydrolytic rate profiles for the two resins. We have also been able to demonstrate temperature-dependence, solvent effects, and inhibitory nature of vanadate ions on the observed rate of hydrolytic reaction aided by the resins. In conclusion, metallated nucleobase resins represent a new class of nucleolytic reagents and these systems have the potential to be further developed for multifarious applications in chemical biology.

Catalysis↗
PubMed2001

Contribution of PTSD/POW history to behavioral disturbances in dementia.

As many World War II and Korean Conflict veterans suffering from posttraumatic stress disorder (PTSD) grow older, increasing numbers will be diagnosed with dementia. We retrospectively analyzed patients with dementia, comparing the behavioral disturbances of those with PTSD to those without PTSD. We hypothesized that due to the additive effect of the neurobiological and behavioral changes associated with PTSD and dementia, the dementia with PTSD group would show more agitation and disinhibition than the dementia without PTSD group. Sixteen patients with diagnoses of dementia and PTSD were matched on age and Mini-Mental States Examination (MMSE) scores to 16 patients with dementia without PTSD. Demographic characteristics, co-morbid diagnoses, global Assessment of Functioning (GAF), Cohen-Mansfield Agitation Inventory (CMAI), and paranoid items of Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale for Schizophrenia (PANSS) were assessed. The patients with diagnoses of dementia with PTSD did not differ significantly in their clinical presentation, hospital course, and condition at discharge from patients with dementia without PTSD. Chi-square analysis showed that significantly more subjects in the PTSD group were prescribed anti-depressants compared to the non-PTSD group. Interestingly, within the PTSD group, the subgroup of patients who were former prisoners of war had a significantly higher mean score for paranoia and significantly less verbal agitation. This pilot study reveals that a diagnosis of PTSD alone is not sufficient to influence behavior in veterans with dementia; however, we also present provocative results that patients with more severe trauma (POW) do have changes in their behavior.

Aged↗
PubMed2001

Endothelin receptor blockade improves endothelial function in human internal mammary arteries.

OBJECTIVE: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. METHODS: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ET(A/B) receptor antagonist, 3 microM), BQ-123 (ET(A) antagonist, 1 microM) and BQ-788 (ET(B) antagonist, 1 microM) using the isolated organ bath apparatus. Percent maximum relaxation (%E(max)) and sensitivity (pEC(50)) were compared between interventions. RESULTS: ACh caused dose-dependent endothelium-mediated relaxation in IMA (%E(max) 43+/-4, pEC(50) 6. 74+/-0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (%E(max) bosentan 60+/-3, BQ-123 56+/-4, BQ-788 53+/-5 vs. control 43+/-4, P<0.05) without affecting sensitivity. The effects of these antagonists were endothelium-specific since endothelium-independent responses to SNP remained unaltered. Furthermore, the beneficial effects were independently and maximally mediated by ET(A) and ET(B) receptors (%E(max) BQ-123 56+/-4 vs. BQ-788 53+/-5 vs. bosentan 60+/-3, P>0. 05). CONCLUSIONS: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.

Acetylcholine↗
PubMed2001

Improved endothelial function with metformin in type 2 diabetes mellitus.

OBJECTIVES: This study was designed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus. BACKGROUND: Abnormalities in vascular endothelial function are well recognized among patients with type 2 (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction. The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported. METHODS: Subjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses to intraarterial administration of endothelium-dependent (acetylcholine), endothelium-independent (sodium nitroprusside) and nitrate-independent (verapamil) vasodilators were measured using forearm plethysmography. Whole-body insulin resistance was assessed on both occasions using the homeostasis model (HOMA-IR). RESULTS: Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil-stimulated (p = 0.40) flows. There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012). CONCLUSIONS: Metformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables. This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus. This has important implications for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus.

Blood Flow Velocity↗
PubMed2001

Hyperinsulinemia superimposed on insulin resistance does not elevate blood pressure.

The role of hyperinsulinemia and insulin resistance in the development of hypertension is an area of much current interest. A central question that remains unanswered is whether exogenous hyperinsulinemia can elevate blood pressure (BP) in the presence of pre-existing insulin resistance. To examine this proposition, we studied the effects of chronic fructose feeding on plasma insulin levels and BP in insulin-resistant Zucker fatty rats and in lean (insulin-sensitive) controls. In addition, vascular responses to norepinephrine in aortae and mesenteric arteries were compared between groups. Zucker fatty rats were hyperinsulinemic, insulin-resistant, yet normotensive when compared with age-matched lean controls. Long term fructose feeding increased plasma insulin levels and BP in the lean group. Strikingly, the fatty rats remained refractory to fructose-induced increases in BP despite exaggeration of hyperinsulinemia. Vascular reactivity assessed in aortae and mesenteric arteries was comparable between groups. These data suggest that, in vivo, the mechanisms of hyperinsulinemia-induced hypertension are not operative in the face of pre-existing insulin resistance in obese Zucker rats.

Animals↗
PubMed2001

Long-term endothelin receptor blockade improves cardiovascular function in diabetes.

To evaluate the potential contribution of endothelin-1 (ET-1) toward the cardiovascular complications of diabetes, the present study examined the effects of chronic ET receptor blockade with bosentan on heart function and vascular reactivity in streptozotocin (STZ)-induced diabetic rats. Wistar rats were divided into four groups: control, control bosentan-treated, diabetic, and diabetic bosentan-treated. After chronic bosentan treatment, cardiac function and vascular reactivity were assessed. Exvivo working heart function was determined in terms of rate of contraction (+dP/dt), rate of relaxation (-dP/dt), and left ventricular developed pressure (LVDP). Contractile responses to ET-1 were determined in isolated superior mesenteric arteries. In addition, ET-1-like immunoreactivity was determined in ventricular and vascular tissues by immunohistochemistry. Cardiac function was depressed in the untreated-diabetic group. Bosentan treatment improved working heart function; hearts from the diabetic bosentan-treated group exhibited improved LVDP and -dP/dt. The contractile responses of mesenteric arteries to ET-1 were exaggerated in the untreated-diabetic group. Long-term bosentan treatment normalized these responses. Immunohistochemical analyses revealed increased ET-1-like immunoreactivity in ventricular and vascular tissues from untreated diabetic rats. These data show the beneficial effects of ET(A/B) receptor blockade on cardiovascular function in STZ-diabetic rats. An altered ET-1 system may contribute toward the pathogenesis of cardiovascular dysfunction in diabetes.

Animals↗