PubMed Health⌕ Search

Biomedical subjects

R Saini

Publications and source records attributed to R Saini.

At least 19 recordsLinked to original sources

Nitric oxide synthase localization in the rat neutrophils: immunocytochemical, molecular, and biochemical studies.

Nitric oxide (NO) modulates diverse functions of polymorphonuclear neutrophils (PMNs), but localization of NO synthase (NOS) and identification of its interacting proteins remain the least defined. The present study discerns subcellular distribution of NOS and caveolin-1, a prominent NOS-interacting protein in rat PMNs. Localization of NOS was explored by confocal and immunogold electron microscopy, and its activity was assessed by L-[3H] arginine and 4,5-diaminofluorescein diacetate (DAF-2DA). Reverse transcriptase-polymerase chain reaction using NOS primers and Western blotting demonstrated the presence of neuronal NOS (nNOS) and inducible NOS (iNOS) in PMNs. Immunocytochemical studies exhibited distribution of nNOS and iNOS in cytoplasm and nucleus, and L-[3H] citrulline formation and DAF fluorescence confirmed NOS activity in both fractions. NOS activity correlated positively with calmodulin concentration in both of the fractions. nNOS and iNOS colocalized with caveolin-1, as evidenced by immunocytochemical and immunoprecipitation studies. The results thus provide first evidence of nNOS and iNOS in the nuclear compartment and suggest NOS interaction with caveolin-1 in rat PMNs.

Animals↗

Comparison of the effects of nebulised and inhaled salbutamol on breathlessness in severe COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often report greater relief of breathlessness with nebulised bronchodilators than with the same medicine administered from a metered dose inhaler (MDI). This suggests that the nebulised medicines may have an effect on breathlessness over and above changes in lung function resulting from bronchodilatation. METHODS: Twenty-four subjects with COPD and breathlessness at rest participated in this randomised, crossover trial. The mean age was 72 years and the mean FEV(1) was 26% of predicted. Subjects were studied on four separate days. On two days they were treated with nebulised salbutamol and on the other 2 days with salbutamol from an MDI and spacer. With each method of delivery, local anaesthetic cream was applied to the face on one day and to the back of the hand on the other. RESULTS: Five minutes after administration of salbutamol the subjects were significantly less breathless with nebulised salbutamol but by 45 min both treatments resulted in equivalent relief. There was no difference between the treatments in the change in FEV(1) or VC and application of local anaesthetic to the face did not influence the response. CONCLUSION: There was a small early benefit with nebulised salbutamol but this was not sustained and was not affected by topical anaesthesia. The benefit of nebulisation does not appear to be large enough to warrant the routine, widespread use of nebulised bronchodilators for the treatment of stable COPD.

Aged↗

Stable genetic transformation of Vigna mungo L. Hepper via Agrobacterium tumefaciens.

Vigna mungo is one of the large-seeded grain legumes that has not yet been transformed. We report here for the first time the production of morphologically normal and fertile transgenic plants from cotyledonary-node explants inoculated with Agrobacterium tumefaciens carrying binary vector pCAMBIA2301, the latter of which contains a neomycin phosphotransferase ( nptII) gene and a beta-glucuronidase (GUS) gene ( uidA) interrupted with an intron. The transformed green shoots, selected and rooted on medium containing kanamycin, tested positive for nptII and uidA genes by polymerase chain reaction (PCR) analysis. These shoots were established in soil and grown to maturity to collect the seeds. Mechanical wounding of the explants prior to inoculation with Agrobacterium, time lag in regeneration due to removal of the cotyledons from explants and a second round of selection at the rooting stage were found to be critical for transformation. Analysis of T(0) plants showed the expression and integration of uidA into the plant genome. GUS activity in leaves, roots, flowers, anthers and pollen grains was detected by histochemical assay. PCR analysis of T(1) progeny revealed a Mendelian transgene inheritance pattern. The transformation frequency was 1%, and 6-8 weeks were required for the generation of transgenics.

Agrobacterium tumefaciens↗

Efficacy and safety of omapatrilat with hydrochlorothiazide for the treatment of hypertension in subjects nonresponsive to hydrochlorothiazide alone.

This multicenter, double-blind study evaluated efficacy and safety of the vasopeptidase inhibitor omapatrilat, which simultaneously inhibits neutral endopeptidase and angiotensin converting enzyme, when given in conjunction with hydrochlorothiazide (HCTZ) to subjects nonresponsive to HCTZ alone. The study enrolled 657 subjects with mild to severe hypertension. After a 2-week placebo lead-in period and a 4-week HCTZ phase, 274 subjects were randomized to receive omapatrilat (10 or 20 mg, electively titrated to 20 or 40 mg, respectively, at week 4 if seated diastolic blood pressure [SeDBP] was > or =90 mm Hg) or matching placebo in addition to 25 mg of HCTZ as continuing therapy. The primary outcome measure was change in SeDBP from baseline to week 8. At week 8, placebo plus HCTZ-adjusted additional reductions in SeDBP in the omapatrilat 10/20 mg and 20/40 mg treatment groups (4 and 5 mm Hg, respectively) were significant (P < .001), as were changes in seated systolic blood pressure in both omapatrilat-treated groups (7 and 10 mm Hg, respectively; P < .001). Seated diastolic blood pressure was normalized (<90 mm Hg) in 38% of subjects in the placebo group compared to 59% and 64% of subjects in the omapatrilat groups (P < or = .008). Adverse events, serious adverse events, and discontinuations attributed to adverse events were infrequent. There were no clinically relevant changes in serum creatinine or potassium. Omapatrilat was effective and well tolerated when added to HCTZ in subjects whose blood pressure was not controlled with HCTZ alone.

Adult↗

In vitro multiplication of Peganum harmala--an important medicinal plant.

The frequency of shoot regeneration and multiplication of P. harmala was influenced by the type of explant and kind and concentration of hormones. Of the various seedling explants, cotyledonary node exhibited maximum shoot regeneration frequency from axillary region on MS medium supplemented with 5 microM BAP. Addition of 0.1 microM NAA enhanced the efficacy of BAP for multiple shoot regeneration as well as improved the growth of shoots. BAP (5 microM) in combination with NAA (0.1 microM) was found to be the optimal for inducing an average of 4-5 shoots per explant in 75% of the cultures within 5 weeks. Replacement of BAP with other cytokinins at equimolar concentration of BAP i.e. 5 microM was not effective in inducing multiple shoots. Regenerated shoots were rooted on MS medium containing IBA (8 microM) with 80% efficiency. The plantlets were successfully established in soil where 80% of them developed into morphological normal plants.

Culture Media↗

The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide.

The long-term safety, tolerability, and antihypertensive effects of irbesartan/hydrochlorothiazide (HCTZ) were assessed in hypertensive patients (seated diastolic blood pressure [SeDBP] 95-110 mm Hg). Patients (n = 1098) completing two randomised, double-blind trials of irbesartan alone, HCTZ alone, irbesartan/HCTZ combinations, or placebo, took 1 year of open-label therapy starting with irbesartan 75 mg/HCTZ 12.5 mg once daily. If target blood pressure (BP) (<140/<90 mm Hg) was not achieved, the dose was titrated sequentially at 2- to 4-week intervals to irbesartan 150 mg/HCTZ 12. 5 mg, then to irbesartan 300 mg/HCTZ 25 mg. If necessary, adjunctive therapies were added. Mean changes in trough seated systolic BP/SeDBP at months 2, 6, and 12 were -19.1/-14.2 mm Hg (n = 941), -20.7/ -15.7 mm Hg (n = 948), and -20.6/-15.6 mm Hg (n = 898), respectively. From months 2 to 12, normalisation rates (trough SeDBP <90 mm Hg) ranged from 75-85% and total responder rates (normalised or >/=10 mm Hg trough SeDBP reduction) ranged from 81-91%, while target BP was achieved in 65-75% of patients. At all time-points, most patients (>/=87%) were receiving irbesartan/HCTZ alone. Eighty-two patients (7.5%) discontinued the study due to adverse events, with half of these events considered unrelated to study medication. There were no reports of serious adverse events related to study medication. Long-term therapy with irbesartan/HCTZ is safe, well tolerated, and maintains normalised BP in >80% of patients.

Aged↗

Comparison of combination of cimetidine and levamisole with cimetidine alone in the treatment of recalcitrant warts.

Various immunomodulating agents have been used in the treatment of recalcitrant warts, but none is uniformly effective. Drugs like cimetidine and levamisole have been tried with varying success rates. Given the different target activities of immunomodulation by levamisole and cimetidine, we questioned whether the combination might be more effective and conducted this double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone. Forty-eight patients with multiple recalcitrant warts were assigned to two treatment groups (A and B) in double-blind fashion. Of the 48 patients, 22 in group A and 21 in group B were able to be evaluated. At the end of therapy, cure rates obtained were 45.5% (10/21) in cimetidine treated patients (group A) and 85.7% (18/21) in combination treated patients (group B). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (P < 0.01). A similar statistically significant result was obtained on using intention to treat analysis (P < 0.02). The rate of regression was faster in group B (average regression period of 7 weeks compared with 10 weeks in group A). The present study demonstrated that the combination of cimetidine with levamisole is more effective than cimetidine alone and is a highly effective therapy for the treatment of recalcitrant warts.

Adjuvants, Immunologic↗

Long-term safety and antihypertensive efficacy of irbesartan: pooled results of five open-label studies.

An analysis of 5 multicenter, open-label studies was conducted to evaluate the long-term safety and efficacy of irbesartan in 1,006 patients with seated diastolic blood pressure (SeDBP) 95-110 mm Hg. Irbesartan monotherapy was started at 75 mg and titrated to 300 mg at 2- to 4-week intervals to achieve normalized blood pressure (SeDBP <90 mm Hg). If normalized BP was not attained with irbesartan 300 mg alone, adjunctive medications could be added. At 12 months of therapy, the mean reduction in seated systolic blood pressure/SeDBP was 21.0/15.8 mm Hg, and 83% (684/821) of patients were normalized. Of those normalized, 64% were receiving irbesartan monotherapy and 86% were receiving irbesartan or irbesartan/hydrochlorothiazide only. No evidence of tachyphylaxis to the antihypertensive effect of irbesartan was noted. Thus, long-term irbesartan therapy, with or without other antihypertensives, achieved and maintained normalized BP in the majority of patients and was well tolerated.

Adolescent↗

The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group.

In a multicenter, double-blind, randomized trial, 178 patients with ambulatory diastolic blood pressure (BP) > or =85 mm Hg and seated diastolic BP (SeDBP) 95-110 mm Hg received either once-daily irbesartan 75 mg/hydrochlorothiazide (HCTZ) 12.5 mg, irbesartan 150 mg/HCTZ 12.5 mg, or placebo for 8 weeks to assess reductions in 24-hour ambulatory BP and office BP. Safety and tolerability of all treatment regimens were also evaluated. BP results and therapeutic response (trough SeDBP normalized to <90 mm Hg) were expressed as change from baseline to Week 8. Mean reductions in 24-hour ambulatory BP and office seated BP for irbesartan/HCTZ combinations were significantly greater compared with placebo (all, p<0.01). More patients were normalized with irbesartan/HCTZ (65%-69%) than placebo (24%, p<0.01). The frequency of adverse events was similar in all groups. Irbesartan/HCTZ given once-daily appears to be a well-tolerated, safe, and effective antihypertensive treatment.

Adult↗

Combination of PUVAsol and topical calcipotriol in vitiligo.

BACKGROUND: A large variety of therapeutic agents are being tried for the treatment of vitiligo, but psoralens continue to be mainstay of treatment although they are not uniformly effective. Recent advances in pathophysiology have established a perturbed calcium homeostasis in affected skin, and melanocytes were shown to express vitamin D3 receptors. OBJECTIVE: The purpose of present study was to determine the efficacy of the combination of PUVAsol with topical calcipotriol in the treatment of vitiligo. METHODS: Nineteen patients with essentially bilateral symmetrical lesions were enrolled in a randomized, double-blind, right/left comparative study of 18 months duration. An oral dose of 0.6 mg/kg 8-methoxypsoralen was given 2 h before exposure to sunlight thrice weekly to all patients. The patients were advised to apply calcipotriol (50 microgram/g) on one side of the body and placebo ointment over the lesions on the other side twice daily. RESULTS: At the end of 6 months, 12 patients (70%) showed marked to complete improvement on calcipotriol-treated sides as compared to 6 patients (35%) showing similar improvement on placebo-treated sides (p <0.05). At the end of treatment, 13 patients (76%) showed marked improvement in calcipotriol-treated lesions whereas 9 patients (53%) showed moderate to marked improvement in placebo-treated lesions. The repigmentation of hands and feet was much better with the combination of PUVAsol and calcipotriol. CONCLUSION: The combination of PUVA and calcipotriol is highly effective and works faster and may be used for shortening the therapy with PUVA in the treatment of vitiligo.

Administration, Topical↗

Management of hypertension: the role of combination therapy.

The complementary action of angiotensin converting enzyme inhibitors and diuretics in the treatment of hypertension has been demonstrated in a number of studies of fosinopril and hydrochlorothiazide (HCTZ). The combination provides a clinically significant reduction in blood pressure while minimizing the dose-dependent adverse effects of HCTZ, such as hypotension and its metabolic effects on plasma lipoproteins, by keeping the dose of each agent to the minimum. Fosinopril has a unique dual mechanism of elimination and can therefore be used in patients with renal impairment. The efficacy of the combination of fosinopril and hydrochlorothiazide compared with placebo and other agents is reviewed in this article. Studies have demonstrated that the combination is effective in the elderly and in renally impaired patients, regardless of severity. In addition, in non-insulin dependent diabetes, antihypertensive effect is achieved without further affecting carbohydrate and lipid metabolism, which is often the case when thiazide diuretics alone are used. A matrix study was performed to evaluate the optimum dose combination to produce blood pressure normalization and minimize side effects. This study evaluated 17 different dose combinations and demonstrated that the lowest dose combination to produce a clinically significant effect was fosinopril 10 mg and HCTZ 12.5 mg. However, a dose-related antihypertensive effect can be seen, giving the option for the use of 20 mg fosinopril for moderately hypertensive patients. Both combination therapy and fosinopril were significantly more effective than HCTZ alone or placebo. The fosinopril/HCTZ combination has also been shown to have a comparable effect to sustained-release nifedipine and propanolol + HCTZ. The studies reviewed here demonstrate that fosinopril/HCTZ combination treatment has a number of advantages over either agent used alone, providing blood pressure normalization in a broad range of hypertensive patients, including diabetic patients and the elderly.

Adult↗