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At least 325 records · Page 18Linked to original sources
PubMed2006

Influence of diabetes on manifestations and treatment outcome of pulmonary TB patients.

OBJECTIVE: To understand the influence of diabetes on the clinical and bacteriological aspects and treatment outcome of pulmonary tuberculosis (PTB) patients. SETTING AND DESIGN: Records of 692 consecutive smear-positive PTB patients admitted to a referral hospital in Riyadh, Saudi Arabia, were reviewed retrospectively. The characteristics of 187 patients with diabetes mellitus (PTB-DM group) were compared to 505 patients without DM (PTB group). RESULTS: In the PTB-DM group, 65.2% of the patients had numerous acid-fast bacilli (AFB) on sputum smear examination compared to 54.1% in the control group (P = 0.008). Among new cases, PTB-DM patients had a lower prevalence of resistance to any anti-tuberculosis drug (6.4% vs. 16.0%, P = 0.007) and achieved higher sputum conversion rates at the end of 3 months of treatment (98.9% vs. 94.7%, P = 0.013). Favourable outcomes (cured/treatment completed), failure, death and default were comparable in both groups (P = 0.7005). CONCLUSIONS: PTB-DM patients have a higher pre-treatment bacillary load, a lower prevalence of anti-tuberculosis drug resistance and achieve slightly higher sputum conversion by the end of 3 months of treatment compared to non-diabetic patients. The association of diabetes does not alter the final treatment outcome among PTB patients.

Adolescent↗
PubMedDate not supplied

Causes and treatment of vitreous hemorrhage.

Vitreous hemorrhage is common, with varied clinical manifestations and causes. The most common causes include proliferative diabetic retinopathy, vitreous detachment with or without retinal breaks, and trauma. Less common causes include vascular occlusive disease, retinal arterial macroaneurysm, hemoglobinopathies, age-related macular degeneration, intraocular tumors, and others. The natural history depends on the underlying cause, and is generally more favorable in eyes without underlying disease. Treatment is directed at the underlying cause, such as laser photo-coagulation for proliferative diabetic retinopathy or for retinal breaks. Occasionally, hemorrhage does not resolve spontaneously and vitrectomy surgery is necessary and beneficial. New strategies for the treatment of vitreous hemorrhage, such as pharmacologic vitreous liquefaction, may be important in the future.

Animals↗
PubMed1983

Antifertility agents. 38. Effect of the side chain and its position on the activity of 3,4-diarylchromans.

In a study of the effect of the substituent on the receptor binding affinity (RBA), estrogenicity, and antiimplantation (AI) activity in trans-3,4-diarylchromans, it has been found that demethylation of trans-2, 2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl]-7-methoxychroman (centchroman, 1) to the corresponding 7-hydroxy compound (7) results in a 20-fold increase in RBA (112%) without any appreciable change in AI activity. On the other hand, absence of the pyrrolidinoethyl group from the 4-phenyl residue (6) leads to a drop in both RBA and AI activity. A chain length of two to three carbon atoms and a pyrrolidino ring appear to be necessary for activity in these compounds. It has been found that while the trans isomers with the tertiary aminoalkoxy side chain in the para position of the 4-phenyl radical were the most active, in the corresponding cis-chromans and chromenes, analogues with this chain in the meta position were most active; the ortho substituted compounds of all these series were inactive. In 3-phenyl-substituted compounds, the trans isomer carrying the p-hydroxy substituent (33) was found to be the most active; the corresponding pyrrolidinoethyl ether (13) showed a lower order of activity. The implication of these observations on the mapping of the different subsites on the receptor has been discussed.

Animals↗
PubMedDate not supplied

Chemoprevention of breast cancer: tamoxifen, raloxifene, and beyond.

Breast cancer is the most common cancer and the second most common cause of cancer death among women in the United States. While nonrandomized studies have reported that prophylactic mastectomy or oophorectomy can significantly reduce the risk of breast cancer, these approaches are unacceptable to the majority of women. Chemoprevention, which is defined as the prevention of cancer by pharmacological agents that inhibit or reverse the process of carcinogenesis, has thus increasingly become the focus of breast cancer prevention efforts. The first-generation selective estrogen receptor modulator (SERM) tamoxifen is the only US Food and Drug Administration- approved drug for breast cancer prevention and reduces the risk of breast cancer by as much as 50% in high-risk women. Raloxifene, a second-generation SERM, also has demonstrated efficacy for breast cancer prevention and is being compared with tamoxifen in a large randomized trial that has recently completed accrual. The aromatase inhibitors (AIs) decrease the incidence of contralateral breast cancer when used in the adjuvant setting and are being evaluated in ongoing primary prevention studies. In addition, a number of novel agents, including antiinflammatory drugs and retinoid derivatives, which appear to be of promise based on preclinical and epidemiological data, are under investigation. Several important challenges remain, including determination of the appropriate dose and duration of treatment when used in the primary prevention setting and development of new research models using surrogate end points for breast cancer incidence and mortality to permit more rapid clinical application of promising new agents.

Antineoplastic Agents, Hormonal↗
PubMed2006

Distribution, transition, adhesion and release of insulin loaded nanoparticles in the gut of rats.

The purpose of this work was to investigate distribution, transition, bioadhesion and release behaviors of insulin loaded pH-sensitive nanoparticles in the gut of rats, as well as the effects of viscosity agent on them. Insulin was labeled with fluorescein isothiocyanate (FITC). The FITC-insulin solution and FITC-insulin nanoparticle aqueous dispersions with or without hydropropylmethylcellulose (HPMC, 0.2%, 0.4%, or 0.8% (w/v)) were orally administered to rats, respectively. The amounts of FITC-insulin in both the lumen content and the intestinal mucosa were quantified by a spectrofluorimeter. The release profiles in the gut were plotted by the percentages of FITC-insulin released versus time. FITC-insulin nanoparticle aqueous dispersion showed similar stomach but lower intestine empty rates, and enhanced intestinal mucosa adhesion in comparison with FITC-insulin solution. Addition of the HPMC reduced the stomach and intestine empty rates, enhanced the adhesion of FITC-insulin to the intestine mucosa. The release of FITC-insulin from nanoparticles in the gut showed an S-shape profile, and addition of HPMC prolonged the release half-life from 0.77 to 1.51h. It was concluded that the behaviors of pH-sensitive nanoparticles tested in gastrointestinal tract of rats and the addition of HPMC were favorable to the absorption of the drug loaded.

Animals↗
PubMed1998

A procedure for Poitou jackass sperm cryopreservation.

We have tried to establish sperm banking for the endangered Poitou donkeys. No successful cryopreservation technique had been described for spermatozoa of this species; our preliminary work indicated that a particular medium and procedure may be effective for cryopreservation of Poitou jackass spermatozoa as evaluated by sperm motility, membrane integrity and pregnancy rate after AI with frozen-thawed semen. We found that glutamine at 80 mM and 10% (v/v) quail egg yolk in a basal medium containing 4% (v/v) glycerol (T2-94 medium) improved the post-thaw total and progressive motility and velocity assessed with the automated analyzer ATS-M. The T2-94 medium also preserved the sperm nuclear, acrosom, and plasma membrane integrity as assessed with the acridine orange method, fluorescein-conjugated Pisum sativum agglutinin (FITC-PSA) lectin procedure, and hypo-osmotic swelling test, respectively. Semen frozen-thawed in T2-94 medium as used to artificially inseminate. 13 Poitou jennies from the beginning of estrus to ovulation during 4 cycles at a rate of one AI per day. Heigh pregnancies and 3 foals were obtained, but only when the glycerol was removed from sperm before AI. We conclude that the cryopreservation of Poitou jackass semen for sperm banking may succeed by using the T2-94 medium and removing the glycerol post-thaw, but before AI.

Acrosome↗
PubMed2006

Apolipoproteins AI and B as therapeutic targets.

Currently the apolipoprotein B:AI ratio integrates information about the potential for cardiovascular disease (CVD) risk reduction better than any other lipid or lipoprotein index. Certainly it could, with benefit, replace serum cholesterol and HDL cholesterol in the estimation of CVD risk. Defining the therapeutic target of statin therapy in terms of serum apolipoprotein B (apo B) rather than LDL cholesterol could also help to optimize statin treatment. Deciding whether a therapeutic response is adequate also requires knowledge of whether there is persisting hypertriglyceridaemia, because this gives an indication of whether small dense LDL is likely to have been satisfactorily reduced. Raising low levels of HDL, probably best measured as apo AI, may also prove to be an important aim of treatment. This is, however, a more complex issue and also depends on the mechanism by which a particular therapy alters HDL levels and on whether the capacity of HDL to perform its anti-inflammatory and antioxidative functions is restored. A meta-analysis of randomized clinical trials of statins in which apo B and apo AI have been reported could provide valuable information.

Anticholesteremic Agents↗
PubMedDate not supplied

Adjuvant hormonal therapy in peri- and postmenopausal breast cancer.

Tamoxifen has been the mainstay of endocrine treatment for early-stage breast cancer in both premenopausal and postmenopausal women for many years. Since 2001, the results of several large, randomized, clinical trials have provided evidence that aromatase inhibitor (AI) therapy, either upfront or in sequence after tamoxifen, improves disease-free survival and, in certain patients, overall survival for postmenopausal patients with hormone receptor-positive breast cancer. Thus far, with relatively short-term follow-up, AIs have been generally safe and well tolerated among the population of patients treated in these adjuvant trials. However, important side effects such as musculoskeletal and bone-related problems, including the risk for osteoporosis and fractures, remain of concern and warrant continued monitoring and follow-up. Several questions regarding the appropriate AI to use and the timing of AI therapy remain unresolved, and ongoing studies will help address these issues. Caution is warranted in the use of AIs in perimenopausal women, including those that develop chemotherapy-induced amenorrhea, and clinical evidence supports the role for AI use in postmenopausal women only. Areas of active investigation include the mechanisms of resistance to endocrine therapy with tamoxifen and AIs and clinical strategies to overcome this resistance.

Antineoplastic Agents, Hormonal↗
PubMed2004

Fulvestrant ('Faslodex')--a new hormonal treatment for advanced breast cancer.

In patients with hormone receptor-positive advanced breast cancer (ABC), endocrine therapy is as effective as cytotoxic chemotherapy but is better tolerated. Most breast cancers are hormone responsive, but eventually develop resistance to individual endocrine agents. However, changing to a different type of endocrine therapy when resistance develops can circumvent this problem and delay the need for cytotoxic chemotherapy. Such chemotherapy can have a major impact on patient's quality of life, and for this reason is generally considered to be a last option for breast cancer patients. Fulvestrant ('Faslodex') is a new type of endocrine therapy with a different mode of action to existing treatments. It is at least as effective as the third-generation aromatase inhibitor (AI) anastrozole or letrozole in the treatment of postmenopausal women with advanced, tamoxifen-resistant breast cancer. Fulvestrant also appears to be effective after treatment with non-steroidal AIs. Fulvestrant is well tolerated and provides a further option in the endocrine treatment of ABC.

Adult↗
PubMed2006

Postmenopausal advanced breast cancer: options for therapy after tamoxifen and aromatase inhibitors.

All patients receiving endocrine treatment for advanced breast cancer (ABC) eventually progress, resulting in a need for new therapies that lack cross-resistance with existing agents. Oestrogen receptor (ER) modulators such as toremifene and raloxifene have poor efficacy following tamoxifen failure, whereas the non-steroidal aromatase inhibitors (AIs), anastrozole and letrozole and the steroidal AI exemestane are effective. Fulvestrant is a new ER antagonist with no agonist effects that is as effective as anastrozole in treating patients who have progressed on tamoxifen. AIs are replacing tamoxifen as first-line treatments for ABC and in the adjuvant setting, necessitating a re-evaluation of optimal sequencing. Preliminary data suggest that tamoxifen, exemestane and fulvestrant have activity in patients who have progressed on non-steroidal AIs and hence could be considered for use in this setting. Due to the apparent lack of cross-resistance between non-steroidal and steroidal AIs, non-steroidal AIs could also be effective following steroidal AI failure. Clinical trials are underway to assess the most appropriate treatment sequence following non-steroidal AI failure, with comparisons of fulvestrant and exemestane of major interest.

Aromatase Inhibitors↗
PubMed2001

Optimal timing and dosage of chemotherapy as a combined treatment with androgen withdrawal in the human prostate LNCaP tumour model.

Although numerous chemotherapeutic agents have been evaluated for patients with advanced prostate cancer, none have demonstrated improved survival benefits. Here, in order to determine whether the efficacy of chemotherapy can be enhanced by changing the regimen, we evaluated the effect of the varied timing and dosage of chemotherapy in combination with androgen withdrawal on time to androgen-independent (AI) progression in the human androgen-dependent LNCaP tumour model. We first demonstrated the synergistic effect of mitoxantrone on induction of apoptosis in LNCaP cells maintained in the steroid hormone-depleted charcoal-stripped media (CSM) compared to those in the standard media. In addition, this synergy was most remarkable during the simultaneous treatment of LNCaP cells with mitoxantrone and CSM compared to the pre- or post-use of mitoxantrone with CSM. LNCaP tumour growth in athymic nude mice and their increase in serum PSA levels were significantly inhibited by the simultaneous injection of mitoxantrone with castration, compared to the administration of mitoxantrone 2 weeks before or after castration. The TUNEL staining revealed that apoptotic cell death was extensively induced in LNCaP tumours treated with simultaneous castration and mitoxantrone compared to tumours treated with the other schedules. Furthermore, nude mice bearing LNCaP tumours were injected with a total of 0.5 mg mitoxantrone divided into 2, 5 and 10 days, with the most significant therapeutic effect and delayed AI progression observed in mice given injection of mitoxantrone for 2 days. These findings suggest that this might be the optimal way to perform cytotoxic chemotherapy and androgen withdrawal simultaneously in patients with advanced prostate cancer and to administer chemotherapeutic agents at high dosage within short intervals.

Androgens↗
PubMed2006

Evaluation of the time-concentration-mortality responses of Plutella xylostella larvae to the interaction of Beauveria bassiana with a nereistoxin analogue insecticide.

Six bioassays were conducted to evaluate the interaction between Beauveria bassiana SG8702 and a nereistoxin analogue insecticide, diammonium S,S'-(2-dimethylaminotrimethylene)di(thiosulfate), which is highly compatible with the fungal biocontrol agent against diamondback moth Plutella xylostella (L.). Second-instar larvae were exposed to sprays of B. bassiana alone (assay 1) at concentrations of 21-38, 157-232 and 822-1133 conidia mm(-2) or together with the insecticide at the low application rates of 5, 10, 25, 50 and 100 microg AI ml(-1) (assays 2-6), and then maintained at 25 degrees C and 12:12 h light:dark photoperiod for daily monitoring of mortality for 8 days. Based on the modelling of the resultant time-concentration-mortality data sets, the fungal agent was highly virulent to P. xylostella with an LC50 decreasing from 269 conidia mm(-2) on day 4 to 107 on day 8. Lower lethal concentrations or shorter median lethal times resulted from fungal sprays including the tested chemical rates; the latter never caused higher mortalities than the fungal treatments alone. The fungal action over 3-7 days after spray was significantly enhanced by including in the fungal sprays the chemical at rates of > or =25 microg ml(-1) for 2.6- to 1756-fold reduction of LC50 values, > or =50 microg ml(-1) for 4- to 274-fold reduction of LC70 values and 100 microg ml(-1) for 9- to 33-fold reduction of LC90 values respectively. These rates were equivalent to 5-20% of the chemical rate labelled for field application. The fungal and chemical interaction outlined above highlights the feasibility of combined formulation or application of B. bassiana and the chemical insecticide for P. xylostella control.

Animals↗
PubMedDate not supplied

Comparison of the actions of the angiotensin-converting enzyme inhibitors enalapril and S-9490-3 in sodium-deplete and sodium-replete spontaneously hypertensive rats.

The hypotensive action of the angiotensin-converting enzyme (ACE) inhibitors enalapril and S-9490-3 was examined in conscious, chronically cannulated Na+-replete and Na+-deplete spontaneously hypertensive rats (SHR) of the Okamoto strain. Blood pressure, plasma ACE activity, plasma renin activity (PRA), and pressor responses to intravenous bolus injections of angiotensin I (AI) were measured over a 24-h period following a single oral dose of ACE inhibitor (0.3, 1.0, and 3.0 mg/kg) or vehicle. S-9490-3 caused a significantly greater hypotensive response and inhibition of plasma ACE and AI pressor responses than enalapril for each dose in both diet groups. Single oral doses of both drugs (3 mg/kg) caused slow, progressive falls in blood pressure which were maximal at 12 h. In contrast, inhibition of plasma ACE was maximal 1 h following the oral dose and returned to control levels over the 24-h period. The inhibition of the pressor response to intravenous AI paralleled, and was significantly correlated with, the inhibition of plasma ACE. There was no correlation between the maximal fall in blood pressure with PRA or with inhibition of plasma ACE activity in either diet group. The hypotensive response to both drugs at the 3-mg/kg dose was greater in Na+-deplete SHR than in Na+-replete animals. Both drugs caused large rises in PRA. The ACE inhibitor S-9490-3 is a significantly more potent hypotensive agent than enalapril in the SHR and a significantly more potent ACE inhibitor in vivo. The hypotensive response to both drugs was dissociated in onset and duration from the inhibition of plasma ACE and AI pressor responses.

Angiotensin I↗
PubMedDate not supplied

Absolute bioavailability of [14C] genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity.

The systemic plasma pharmacokinetics of genistein were determined in rats to evaluate the absolute oral bioavailability and make comparison with similar data in the literature derived from humans subjects. The plasma concentrations of genistein, genistein glucuronide and carbon-14 were determined by LC-MS/MS and liquid scintillation counting following oral and intravenous dosing with [14C]genistein (4 mg kg(-1) body weight). The absorption of total radioactivity from the gut, (parent compound and metabolites), was 56 and 111% in male and female rats, respectively. In contrast, the absolute oral bioavailability of genistein in male and female rats was 7 and 15%. There was a significant (P<0.001) difference between Cmax of genistein after intravenous (6921 and 4392 ng/ml) and oral (21 and 22 ng/ml) dosing in male and female rats, respectively. After oral administration, the concentration profile of genistein glucuronide in plasma greatly exceeded that of parent compound during the absorption/distribution phase suggesting extensive first pass metabolism, and provided evidence of entero-hepatic circulation. Selective plasma analysis by LC-MS/MS, without prior enzymatic hydrolysis, enabled ready discrimination between parent and conjugated metabolites and prevented gross overestimation of genistein bioavailability. Pharmacokinetic parameters Cmax, Tmax and AUC were similar to those reported in humans, which supports the use of the rat model for genistein toxicity studies.

Animal Feed↗
PubMed2006

Optimizing the use of aromatase inhibitors in adjuvant therapy for postmenopausal patients with hormone-responsive early breast cancer: current and future prospects.

PURPOSE: Five years of tamoxifen treatment after primary surgery has had a significant impact on outcomes for women with early breast cancer, but the third-generation aromatase inhibitors (AIs) are now challenging tamoxifen as the gold standard endocrine adjuvant treatment. Results from two large, phase III, early adjuvant studies have indicated that the AIs letrozole and anastrozole offer greater protection against recurrence than tamoxifen in upfront substitution strategies in the first 5 years after surgery. Similarly, changeover to an AI (exemestane or anastrozole) after 2-3 years of tamoxifen has been shown to offer greater protection against recurrence than 5 years of tamoxifen. More than 50% of early breast cancer recurrences occur five or more years after surgery. Letrozole has been shown to offer greater protection against recurrence than placebo in the 5 years after a standard course of tamoxifen. The safety implications of treatment with these potent AIs for 5 years or more are being closely monitored. Anticipated effects of estrogen deprivation on bone health may be treatable with bisphosphonates, and this strategy is under investigation. Effects on the cardiovascular system, and other estrogen-sensitive systems such as the central nervous system, are currently unclear and further results are awaited. CONCLUSION: Current evidence indicates that the third-generation AIs will improve outcomes for many women with early breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed1995

Adenosine analogues modulate the incidence of sleep apneas in rats.

The effects of adenosine A1 and A2 agonists on spontaneous central sleep apneas in rats have been examined by simultaneously monitoring sleep and respiration in freely moving unanesthetized animals. Intraperitoneal administration of 1.0 mg/kg of the A1 receptor agonist R(-)N6-L-(2-phenyl-isopropyl)adenosine (L-PIA) and 150 and 300 micrograms/kg of 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine hydrochloride (CGS 21680), a selective A2 agonist, decreased the apnea index (AI) during sleep. Within a sleep period, AI increased over time in both control and drug-treated animals. For both agonists, doses effective in reducing AI also significantly reduced sleep efficiency.

Adenosine↗
PubMed2005

Interaction of daunomycin antibiotic with human serum albumin: investigation by resonant mirror biosensor technique, fluorescence spectroscopy and molecular modeling methods.

Daunomycin (DM) is a clinically used antitumor anthracycline antibiotic, which is transported primarily by human serum albumin (HSA) in the blood. Binding characteristics are therefore of interest for both the pharmacokinetics and pharmacodynamics of DM. A new optical biosensor technique based on the resonant mirror was used to characterize interaction of DM with HSA at different temperatures and the affinity constants were obtained. The HSA-DM interaction is exothermic with having favorable enthalpy and entropy followed by the integrated van't Hoff equation analysis. Fluorescence studies showed that DM has an ability to quench the intrinsic fluorescence of HSA through a static quenching procedure according to the Stern-Volmer equation and DM displays a pH-dependent binding affinity to HSA. Molecular modeling calculations showed that the DM binds HSA to a non-classical drug binding site and further analysis of the binding site of DM within the HSA molecule suggested that hydrophobic contacts, hydrogen bond formation and electrostatic interactions account for the binding of DM.

Anti-Bacterial Agents↗