Drug-Drug Interactions in Patients with Breast Cancer

The research paper investigates the intricate landscape of drug-drug interactions (DDIs) within the context of breast cancer treatment, with a particular focus on the elderly population and the use of complementary and alternative medicine (CAM). The study underscores the heightened susceptibility of elderly patients to DDIs due to the prevalence of polypharmacy and the widespread utilization of CAM among breast cancer patients. The potential ramifications of DDIs, encompassing adverse drug events and diminished treatment efficacy, are elucidated. The paper accentuates the imperative for healthcare providers to comprehensively understand both conventional and CAM therapies, enabling them to provide patients with informed guidance regarding safe and efficacious treatment options, culminating in enhanced patient outcomes.

Antimicrobial and antispasmodic activity of leaf extract and fractions of Stachytarpheta cayennensis

Objective:To investigate the antimicrobial activity of the methanol leaf extract(ME),n-hexane fraction(HF),ethylacetate fraction(EF) and methanol fraction(MF),of Stachytarpheta cayennensis C.Rich(verbenaceae) as well as to ascertain the antispasmodic effects of the ME and the various fractions(HF,EF and MF) on acetylcholine(Ach) and histamine(H) induced contractions on isolated guinea pig ileum.Methods:The in vitro agar well diffusion method was used for the antimicrobial studies while the isolated tissue method was employed for the antispasmodic test. Organisms used were all clinical isolates of Bacillus subtilis,Staphylococcus aureus,Pseudomonas aeruginosa,Salmonella paratyphi,Candida albicans and Aspergillus niger.Results:The extract and fractions exhibited dose dependent inhibition against all the bacteria tested and also exhibited insignificant antifungal activity against Candida albicans and Aspergillus niger.The minimum inhibitory concentration(MIC) of the extract and fractions(mg/mL) on Bacillus subtilis, Staphylococcus aureus,Pseudomonas aeruginosa and Salmonella paratyphi respectively were ME 5.62,14.12,22.38,2.11;EF 1.25,6.30,9.40,9.40 and MF 3.98,8.81,39.80,21.13.The n-hexane fraction exhibited MIC of 1.07 mg/mL against only Bacillus subtilis.The extract and fractions exhibited significant(P【 0.05) dose dependent attenuation of contractions induced by acetylcholine and histamine on isolated guinea pig ileum.Concentrations of the extract and fractions(μg/mL) which evoked 50%inhibition of maximal response exhibited by Ach were ME 0.64,HF 0.16,EF 0.08 and MF 0.15,while that of histamine included ME 5.12,HF 0.16,EF 0.04 and MF 0.64.Preliminary phytochemical studies on the extract and fractions indicated the presence of carbohydrates,alkaloids,saponins,flavonoids,steroids and terpenoids.Conclusions: The extract and fractions of Stachytarpheta cayennensis possessed both antibacterial and antispasmodic effects confirming the claimed use in folkloric medicine for wound healing and gastrointestinal ulceration.

Effect of hyperthermia on calbindin-D 28k immunoreactivity in the hippocampal formation following transient global cerebral ischemia in gerbils

Calbindin D-28K （CB）, a Ca2＋-binding protein, maintains Ca2＋ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We inves- tigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei （NeuN） and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia （39.5 ＋ 0.2~C） was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neu- ronal damage/death in the pyramidal layer of CA1-3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreac- tivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immu- noreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.

Multiple facets of poly(ADP-ribose) polymerase-1 in neurological diseases

The highly conserved abundant nuclear protein poly （ADP-ribose） polymerase-1 （PARP-1） is activated by DNA damage. PARP-1 activation is associated in DNA repair, cell death and inflammation. Since oxidative stress induced robust DNA damage and wide spread inflamma- tory responses are common pathologies of various CNS diseases, the attention towards PARP-1 as a therapeutic target has been amplifying. This review highlights the multiple roles of PARP- 1 in neurological diseases and po- tential of PARP- 1 inhibitors to enter clinical translation.

Effect of Atorvastatin on Expression of Peroxisome Proliferator-activated Receptor Beta/delta in Angiotensin Ⅱ-induced Hypertrophic Myocardial Cells In Vitro

Objective To explore the effect of atorvastatin on cardiac hypertrophy and to determine the potential mechanism involved. Methods An in vitro cardiomyocyte hypertrophy from neonatal rats was induced with angiotensinⅡ(Ang Ⅱ) stimulation. Before AngⅡ stimulation, the cultured rat cardiac myocytes were pretreated with atorvastatin at different concentrations(0.1, 1, and 10 μmol/L). The following parameters were evaluated: the myocyte surface area, 3H-leucine incorporation into myocytes, m RNA expressions of atrial natriuretic peptide, brain natriuretic peptide, matrix metalloproteinase 9, matrix metalloproteinase 2, and interleukin-1β, m RNA and protein expressions of the δ/β peroxisome proliferator-activated receptor(PPAR) subtypes. Results It was shown that atorvastatin could ameliorate Ang Ⅱ-induced neonatal cardiomyocyte hypertrophy in the area of cardiomyocytes, 3H-leucine incorporation, and the expression of atrial natriuretic peptide and brain natriuretic peptide markedly. Meanwhile, atorvastatin also inhibited the augmented m RNA level of several cytokines in hypertrophic myocytes. Furthermore, the down-regulated expression of PPAR-δ/β at both the m RNA and protein levels in hypertrophic myocytes could be significantly reversed by atorvastatin treatment. Conclusions Atorvastatin could improve AngⅡ-induced cardiac hypertrophy and inhibit the expression of cytokines. Such effect might be partly achieved through activation of the PPAR-δ/β pathway.

Antimalarial activities of butanol and ethylacetate fractions of Combretum nigricans leaf

Objective: To evaluate the antimalarial activity of the ethylacetate and butanol fractions of Combretum nigricans(C. nigricans) leaf extract in mice. Methods: C. nigricans solvent(butanol and ethylacetate) fractions were screened for their phytochemical constituents using standard procedures illustrated by Harborne and Evans. The Peters' 4-day suppressive test against early malaria infection, Rane's curative test against established malaria and prophylactic test for residual activity were employed for evaluating the antimalarial potential in mice. Results: The phytochemical screening revealed the presence of alkaloids, terpenoids, saponins, and flavonoids in both fractions at different intensity. Both fractions exhibited significant antimalarial activity in all test models(P<0.05). The ethylacetate fraction of C. nigricans had better chemosuppressive and curative effects compared to the butanol fraction, which however, elicited a better chemoprophylactic effect. The chemosuppressive effect of C. nigricans ethylacetate fraction(200-800 mg/kg) was 77.6%, 69.1% and 86.1%; curative effect was 62.3%, 71.3% and 72.4%; while the chemoprophylactic activity was 32.1%, 48.6% and 61.2% respectively. C. nigricans butanol fraction(200-800 mg/kg) had 40.3%, 54.1% and 69.1% chemosuppression; 26.2%, 36.9% and 34.5% curative effect; and 48.4%, 70.0% and 87.4% chemoprophylaxis. Conclusions: Both solvent fractions of C. nigricans possess antimalarial activity, and may be useful at different stages of malaria therapy.

Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway

Objective:To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule(EtAc-LME) in MKN-74,NUGC gastric cancer cells and non cancerous gastric mucous cells(GES-1),and to explore the mechanism of EtAc-LME induced apoptosis.Methods:The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases,PARP cleavage,expression of cytochrome-c (Cyt-c) was determined by western blotting,mRNA expression of Bcl-2,Bax by RT-PCR,loss of mitochondrial potential using DiOC6 dye,annexin binding assay and its influence on cell cycle arrest by flow cytometry.Results:The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells(NUCC and MKN-74) compared to normal gastric cells(GES-1),suggesting more specific cytotoxicity to the malignant cells.Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.Conclusions:The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.

The Possible Role of the Incretin Enhancer Sitaglipten, in Renal Ischemic Reperfusion Injury in Type 2 Diabetes Mellitus

Background: Diabetes mellitus (DM) especially type 2 is a major health problem and diabetic nephropathy is the main cause of end stage renal disease (ESRD). Renal ischemia/reperfusion (I/R) injury is common in diabetic patients. Recent studies reported increased vulnerability of kidneys to I/R injury in diabetic rats. In view of the reported efficacy of incretin enhancer on I/R injury. Aim: This study was designed to assess the effect of sitaglipten on renal I/R in type 2 diabetes mellitus . Methods: Type 2 DM in rats were induced by administration of nicotinamide (230 mg/kg, i.p.), 15 min prior to the single dose of streptozotocin (65 mg/kg, i.p.). Renal I/R were performed in both diabetic and normal rats. Results: The lipid peroxidation, xanthine oxidase activity, and nitric oxide levels were significantly increased after I/R in diabetic rats compared to I/R in normal rats. Antioxidant enzymes such as glutathione, superoxide dismutase, catalase, and glutathione peroxidase were significantly reduced after I/R in diabetic rats compared to normal rats. Sitaglipten treatment significantly normalized these biochemical parameters compared to diabetic I/R rats. Serum TNF-α level and myeloperoxidase activity were also significantly normalized after administration of sitaglipten. Furthermore, treatment with sitaglipten (10 mcg/kg) had preserved the normal morphology of the kidney compared to I/R performed in diabetic rats. Conclusion: Sitaglipten protects exaggerated renal I/R injury in type 2 DM. These findings have major implication in the treatment of ischemic injury that is prone to develop in DM.

Urinary Extraction of Oxidative Damage in Carpet Weavers

Nearly 8.5 million people in Iran directly or indirectly make a living from hand-made carpet weaving industry. Ongoing work, poor postures, breathing problems and skin irritations are among factors affecting the health, safety and wellbeing of those involved in this industry. Hence, considering such factors seem to improve the quality of carpet as a valuable cultural commodity and expand its export. Accordingly, this study investigates the oxidative stress biomarkers among involved and non-involved people in the hand-made carpet industry. 25 carpet maker and 25 ordinary people (not involved in carpet industry) who had been matched for age and sex were selected as study groups. The level of oxidative stress biomarkers such as antioxidant capacity, total thiols and catalase were measured among subjects, and finally the biomarkers were compared between the two groups. To compare the oxidative stress biomarkers in two groups, Independent Sample T Test was used. The mean levels of total antioxidant capacity showed no significant difference between the two groups (0.05 p-value). In conclusion, carpet weaving industry induces oxidative stress and natural antioxidant may be considered beneficial for the protection of oxidative damage in such subjects.

The Role of Recruitment and Retention in Clinical Trials

It is evident that both recruitment and retention play critical roles in clinical trials. Recruitment and retention models are beginning to be analyzed worldwide in an effort to assess how to conduct studies more efficiently, all the while, allowing researchers to provide sound and ethical data to help advance medicine through clinical studies. Sponsors and sites have recognized that clinical trial enrollment must become more diverse and inclusive. In this review, we address the important topics of recruitment and retention in clinical trials. Specifically, the obstacles in regard to recruiting vulnerable populations. Methodologies to improve both the understanding of the study population and community engagement are outlined. In particular, newer strategies such as use of social media and more reliable strategies such as trust and relationship building are described in detail. A strong focus on recruitment is becoming widely recognized as being of such importance that consideration is given to this key component even during initial protocol development. Attention to recruitment and retention in the strategic planning process of clinical trials can mitigate enrollment issues that clinical researchers are experiencing.

Pharmacological evaluation of a novel enhydrazone ester (CEE-1) as a dual inhibitor of the release of pro-inflammatory cytokines and prostanoids from human monocytes

CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate)—a novel enhydrazone ester, was tested in vitro for anti-inflammatory activity against the release of pro-inflammatory cytokine and prostanoid from lipopolysaccharide-activated human monocytes or human monocytic cell line (U937). The effects were compared with those of standard anti-inflammatory drugs dexamethasone and indomethacin. CEE-1 potently and strongly inhibited the release of both tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). The concentrations producing 50% inhibition (IC50 values) were 2.0 μM and 2.4 μM for TNF-α and PGE2, respectively. At 30 μM, the drug achieved almost complete inhibition of both mediators. Dexamethasone had similar effects but indomethacin inhibited only the PGE2 release, and although CEE-1 was less potent than these two drugs, it had comparable efficacy. The compound appeared to act, at least, in part by inhibiting the up-regulation of the mRNA for TNF-α as well as that of the prostanoid-synthetic enzyme, cyclo-oxygenase-2 (COX-2). However, like dexamethasone, but unlike indomethacin, CEE-1 did not affect COX-2 enzyme function. Thus, the profile of activity of CEE-1 is similar to that of steroids rather than the non-steroidal anti-inflammatory drugs. Structure-activity study showed that the presence of a simple aromatic ring attached via an NH-NH group was critical for activity. At the concentrations that completely inhibited mediator release, the compound displayed no significant in vitro toxicity on the cells. These results show that CEE-1 is a dual inhibitor of the release of cytokines and prostanoids, and therefore could be a potential alternative to steroids in the treatment of inflammatory diseases.

Pharmacokinetics Evaluation of Nimotuzumab in Combination with Doxorubicin and Cyclophosphamide in Patients with Advanced Breast Cancer

EGFr （Epidermal growth factor receptor） overexpression has been detected in many tumors of epithelial origin, specifically in breast cancer and it is often associated with tumor growth advantages and poor prognosis. The nimotuzumab is a genetically engineered humanized MAb （monoclonal antibody） that recognizes an epitope located in the extracellular domain of human EGFr. The aim of this study was to assess the pharmacokinetics of nimotuzumab in patients with locally advanced breast cancer who are receiving neoadyuvant therapy combined with the AC chemotherapy regimen （i.e., 60 mg/m2 of Doxorubicin and 600 mg/m2 of Cyclophosphamide in 4 cycles every 21 days）. A single center, non-controlled, open Phase I clinical trial, with histopathological diagnosis of locally advanced stage III breast cancer, was conducted in 12 female patients. Three patients were enrolled at each of the following fixed dose levels： 50, 100, 200 and 400 mg/week. Multiple intermittent short-term intravenous infusions of nimotuzumab were administered weekly, except on weeks 1 and 10, when blood samples were drawn for pharmacokinetic assessments. Nimotuzumab showed dose-dependent kinetics. No anti-idiotypic response against nimotuzumab was detected in blood samples of participants. There was not interaction between the administration of nimotuzumab and chemotherapy at the dose levels studied. The optimal biological doses ranging were estimated to be 200 mg/weekly to 400 mg/weekly.

Combination of Paracetamol and the Glutathione Depleting Agent Buthionine Sulfoximine Show Differential Effect on Liver Cancer Cells and Normal Hepatocytes

Background: Paracetamol exerts toxic effects on liver cells through its metabolism into N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with cellular glutathione (GSH). Once GSH is depleted, NAPQI stimulates a range of oxidative reactions that result in cell necrosis. The aim of the present investigation is to find a new strategy that would selectively protect normal hepatic tissues and sensitize liver cancer cells to the toxic effects of paracetamol or its metabolite. This may lead to the development of a targeted therapy for liver cancer. Methods: The anti-proliferative effects of paracetamol and buthionine sulfoximine BSO (a glutathione depleting agent) alone and in combination on the liver cancer cells HepG2 and normal rat hepatocytes were investigated by sulphorhodamine-B assay. Effects on cell cycle regulation and induction of apoptosis were tested by flow cytometry. The level of prostaglandin expression was measured by ELISA. Results: The present study showed that both agents alone or in combination have anti-proliferative effects on both cell types. Surprisingly, BSO showed a cytoprotective effects on normal hepatocytes treated with high concentrations (1.75 and 2 mM) of paracetamol. This was confirmed by cell cycle analysis that recorded decreased fraction of sub-G1 cells indicating reduction of apoptosis in normal hepatocytes. Analysis of prostaglandin E2 revealed differential effects of paracetamol on normal and liver cancer cells. A significant increase in PGE2 level over the control was observed in normal hepatocytes whereas a significant decrease was seen in HepG2 cells after treatment with paracetamol. Conclusion: These results indicate that combination of paracetamol/BSO has differential effects on liver cancer cells and normal hepatocytes, which opens the avenue for a new effective and selective combination for management of liver cancer.

An emerging role for Hippo-YAP signaling in cardiovascular development

The Hippo signaling pathway was originally discovered in Drosophila and shown to be critical for organ size control and tumorigenesis. This pathway consists of a cascade of kinases and several adaptors that lead to the phosphorylation and inhibition, through nuclear exclusion, of the transcriptional cofactor Yorkie in Drosophila or YAP （yes associated protein） in mammals. Recent studies demonstrate that cardiac-specific deletion of the Hippo pathway kinase Mst （STE20-1ike protein kinases） co-activator WW45 （WW domain-containing adaptor 45）, Mstl, Mst2, or Lats2 （large tumor suppressor homologue 2） in mice result in over-grown hearts with elevated cardiomyocyte proliferation. Consistent with these observations, over-expression of YAP in the mouse embryonic heart increases heart size and promotes cardiac regeneration and contractility after myocardial infarction by inducing cardiomyocyte proliferation, whereas deletion of YAP in the mouse heart impedes cardiomyocyte proliferation, causing myocardial hypoplasia and embryonic or premature lethality. YAP has also been shown to play an important role in the vascular system. Specific-deletion of YAP from vascular smooth muscle cells in mice results in aberrant development of large arteries with a hypoplastic arterial wall phenotype. Hippo-YAP signaling cross-talks with other signaling pathways such as IGF （insulin-like growth factor） and Wnt signaling to promote heart growth by increasing expression of cell cycle genes. The purpose of this review is to summarize these recent findings and discuss potential diagnostic or therapeutic strategies in cardiovascular system based on manipulating the Hippo-YAP signaling.

eIF3 p170与肺癌化疗相关性研究及对肺癌细胞药物敏感性的影响

AIM: To evaluate the expression of eukaryotic initiation factors 3(eIF3) subunit 170 (eIF3 P170) in lung cancer tissues and its association with chemotherapy response of lung cancer. METHODS: 31 paraffin imbedded slices of lung cancer tissue from fiberscope diagnosis, 20 samples of benign lung tissues from inflammatory pseudotumor and bronchiectasis, and 10 samples of normal lung tissues from surgical operation were collected. The protein expression of eIF3 p170 in lung-cancer tissues, benign lesion tissues, and normal lung tissues were determined by immunohistochemical staining. RESULTS: The positive ratio of eIF3 p170 expression in lung cancer tissues is higher than those in normal and benign tissues, the lung cancer patients with a higher expression level of eIF3 p170 seems to be more sensitive to chemotherapy. Here, we also found that down-regulation of expression of eIF3 p170 could inhibit the growth of human lung adeno-carcinoma cell A549 cells and decrease the sensitivity of A549 to cisplatin. CONCLUSION: Our data suggest that eIF3 p170 may be involved in the pathogenesis of lung cancer and it appears to be associated with chemotherapy response of lung cancer.

Aspirin and Blood Glucose and Insulin Resistance

Background: Diabetes mellitus (DM) is a disorder in which blood sugar levels are abnormally high because either absolute or relative insulin deficiency. Treatment of diabetes involves diet, exercise, education and for most people, drugs. Oral antidiabetic drugs and/or insulin doses may be affected by co-administration of many drugs including aspirin. Dose adjustments may be necessary. The pain killer effect of aspirin is best known for its effects on the two cyclooxygenase enzymes (COX1 & COX2), but, recently, aspirin could specifically inhibit the protein I-kappa-β-kinase beta (IKK-beta). This kinase is used for its role in the cascade of signals that activate the nuclear factor kappa-b (NF-kappa-B) family of cellular genes which regulate inflammatory and immune responses. Now, it turns out that IKK-beta also works in another pathway to contribute to insulin resistance by interfering with insulin signaling. Objective: In view of the recent rodent data demonstrating a potentially important role of IKKβ in mediating insulin resistance and the ability of salicylates to inhibit IKKβ activity, we decided to examine the role of different doses of aspirin (low, moderate and high) in experimentally induced diabetic rats. Materials and Methods: DM in rats were induced by administration of nicotinamide (NAD), 15 min prior to the single dose of streptozotocin STZ i.p. Ninety male albino rats were used in this study. They were divided into 6 main groups. The first was served as control which receives no medications. The second group was diabetic induced rats as mentioned above. The third group was controlled by insulin after induction of D.M. Groups from the fourth to the six consist of 20 diabetic induced rats and further subdivided into rats taking either aspirin alone in different doses (low, moderate or high) or aspirin and insulin. At the end of the protocol, fasting blood sugar level (FBS), glycosylated hemoglobin (HBA1c%), total serum proteins, C-peptide, lipid profile and C-reactive proteins were measured. Results: Different doses of aspirin showed that moderate and to a greater extent high dose aspirin administration to diabetic rats have greater impact on fasting blood glucose levels whether treated with insulin or not. Again, HBA1c% in diabetic rats treated with insulin and receiving HDA was lower than diabetic rats treated with insulin only or even taking LDA in addition. On the contrary, different doses of aspirin (LDA, MDA&HDA) administration to diabetic rats have no any influence on HBA1c% as compared to normal non-diabetic rats. TGs in diabetic rats receiving MDA alone was elevated as compared to normal non-diabetic rats. Again, moderate and HDA in diabetic rats not taking insulin had high TGs level as compared to diabetic rats treated with insulin only. Conclusion: The study concluded that the inflammatory pathways hold a substantial part in insulin resistance in type 2 DM. The influence of salicylate compounds on insulin sensitivity is multifactorial especially in high doses, and involves both beneficial and deleterious effects depending on the species and experimental model studied.

Fractures in Parkinson’s Disease

Parkinson’s disease is a neurodegenerative disorder that is common in older people and is highly associated with depression, anxiety, apathy, psychosis, cognitive impairment, imbalance and sleep disturbances. These patients have an increased risk of fracture compared to the general population. Comprehensive searches of databases are performed to identify reviews about the risk of fractures in this disease. Parkinson’s patients are at increased risk for low bone mineral density due to the effect of drugs, Parkinson’s disease and age factor, leading to an increased risk of falling down and fractures, especially in the hip. So, improved and innovative treatments with the focus on minimizing inadvertent bone resorption with anti-Parkinson’s disease medication will be highly effective in reducing fear of the disease and providing the patient with a better quality of life.

Chronic Alcohol Consumption Affects Serum Enzymes Levels in the HIV-Infected Patients on Stavudine (d4T)/Lamivudine (3TC)/Nevirapine (NVP) Treatment Regimen

Chronic alcohol use is a common problem globally among the HIV-infected patients on ARV treatment regimens, leading to severe liver damage and increase in serum enzymes. The study determined effect of chronic alcohol intake on serum enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)) in HIV-infected patients on d4T/3TC/NVP treatment regimen in Uganda using the WHO alcohol use disorders’ identification test (AUDIT) tool and chronic alcohol use biomarkers (ALT, AST, GGT, AST/ALT ≥ 2.0 and mean corpuscular volume (MCV)). A case control study using repeated measure design with serial measurements model was used. Alcohol use biomarkers were used to standardize the gender differences in alcohol use. A total of 41 patients (21 alcohol group and 20 control group) were followed up for 9 months with blood sampling done at 3 month intervals. The serum enzymes’ levels were determined by using the Cobas Intergra 400 Plus analyzer system. The mean GGT levels were higher in chronic alcohol use group as compared to control group in both groups. The levels were above reference ranges during 6 month and three times higher during 9-month follow-up period for both chronic alcohol use self reporting WHO AUDIT tool and biomarkers’ groups. Generally, the mean AST, ALT and AST/ALT levels were slightly higher in alcohol use group as compared to control group and were slightly higher in both groups as compared to reference ranges during the 9 month follow-up period. Chronic alcohol consumption by HIV-infected patients on d4T/3TC/NVP drug regimen increased GGT and AST/ALT serum enzyme levels and hence was used as chronic alcohol use biomarkers.

<i>Low Dose</i>Irbesartan Has a Renoprotective Effect as High Dose Ramipril in Diabetic Rats Treated with Insulin

Objectives: The aim of this study is to compare the efficacy of the anti-angiotensinic drug, ramipril and irbesartan on the vascular protection of kidneys of streptozotocin (STZ)-induced diabetic rats (DR). Methods: 110 male albino rats were divided into 7 main groups. Group-1 (10 normal control rats;NC). Group-2 (10 rats) was injected intra-peritoneally with STZ (Diabetic Rats;DR). Group-3 (10 DR) is controlled by insulin. Groups 4 to 7 (20 DR), each is subdivided into two subgroups that received either low or high dose of ramipril or irbesartan with or without insulin. Two months post treatment, rat-tail blood was collected to measure: Fasting blood sugar, HbA1c, total serum proteins, albumin and lipid profiles. Urine was collected to measure albuminuria. Kidneys were isolated for histopathological study. Results: Biochemically, both ramipril and irbesartan (without insulin) lowered albumin concentration in urine samples especially at high doses. Histopathologically, there is no beneficial response of both drugs without insulin. Combination of insulin together with either drug has beneficial effects biochemically and histopathologically at high doses. Low dose irbesartan only has renoprotective effect in DR treated with insulin. The other biochemical parameters showed negligible response to both drugs. Conclusion: Low dose irbesartan and high doses of both drugs have renoprotective effect in DR treated with insulin.

Effect of Salvia officinalis Hydroalcoholic Extract on Vincristine-induced Neuropathy in Mice

AIM:Vincristine is one of the most commonly used chemotherapeutic drugs to treat a variety of malignant diseases,including leukemia and lymphoma.Studies have shown that vincristine cause painful effects,whereas Salvia officinalis(SO) showed analgesic and anti-inflammatory effects.The aim of this study is to investigate the effects of the SO hydro-alcoholic extract on vincristine-induced peripheral neuropathy in mice in comparison with morphine.METHODS:Experiments were performed on 60 NMRI male mice weighing 25-30 g divided into six groups.The individual groups received normal saline,SO hydro-alcoholic extract,vincristine,SO hydro-alcoholic extract and vincristine(12 days before formalin test),morphine,and vincristine and morphine,respectively.The injected hind paw biting and licking was measured in a 5-minute interval for one hour.RESULTS:The results showed that formalin induce significant(P < 0.05) pain responses(the first phase:0-5 min and the second phase:15-40 min after injection).Administration of SO extract before formalin test showed significant(P < 0.05) decrease of pain response in the second phase.Administration of vincristine caused significant(P < 0.05) increase in the second phase of pain response.Injections of SO extract and vincristine showed that SO significantly(P < 0.05) decrease the second phase of vincristine-induced pain.Morphine decreased vincristine-induced pain in the first and second phase of formalin test significantly(P < 0.05).In comparison,morphine showed analgesic effects in the first phase and SO extract showed significant(P < 0.05) anti-inflammatory effects in the second phase of formalin test.CONCLUSION:Both SO and vincristine showed analgesic and painful neuropathic effects,suggesting that SO extract could be useful in the treatment of vincristine-induced peripheral neuropathic pain.