Pharmaceutical Sciences
Volume:26 Issue: 3, Sep 2020

Recently a number of trials investigated the effect of N-acetylcysteine (NAC) administration on inflammatory markers and homocysteine (Hcy). However, their findings are controversial. The aim of this paper is to present a meta-analysis and give a review of all randomized controlled trials (RCTs) in order to determine the effects of NAC on inflammatory markers and Hcy.

An electronic search was conducted using PubMed, Scopus, Cochrane Library, Google scholar and Web of Science databases from inception until April 2019. A study quality assessment was performed using the Jadad scale and heterogeneity between studies was statistically computed using Cochrane’s Q test and I-square (I2). Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size.

Out of 1115 potential citations, 10 studies (reported 13 effect sizes for different parameters) met the inclusion criteria and were eligible for this meta-analysis. NAC supplementation resulted in a significant reduction in Hcy levels (WMD: -2.05; 95% CI: -3.73, -0.37). NAC administration did not affect C-reactive protein (CRP) levels (WMD: 0.06; 95% CI: -0.21, 0.34), tumor necrosis factor-α (TNF-α) levels (WMD: 0.07; 95% CI: -0.27, 0.40), and interleukin 6 (IL-6) (WMD: -0.23; 95% CI: -1.23, 0.77).

It could be concluded that this meta-analysis of RCTs demonstrated that NAC administration to various patients significantly improved circulating Hcy, but did not affect CRP IL-6 and TNF-α levels.

Prevention and management of type 2 diabetes mellitus (T2DM), as a major, non-communicable disease with increasing prevalence, is one of the major human challenges. The aim of this systematic review is to summarize current studies about the potential roles of taurine in T2DM, to identify knowledge gaps and to provide recommendations for the way forward.

The literature search was performed in PubMed, SCOPUS, Embase, ProQuest and Google Scholar electronic databases to December 2019. All studies investigating the impacts of taurine in T2DM which met the inclusion criteria were eligible.

Out of 1381 articles found in the search, 12 were included. Findings of taurine supplementation on glycemic control in T2DM showed improving effect of taurine on fasting and postprandial blood glucose, serum insulin level, insulin resistance, function of beta cells, and insulin sensitivity. But, the results for Hemoglobin A1c and homeostatic model assessment-insulin resistance (HOMA-IR) were contradictory. Also, taurine reduced total cholesterol, TG, and low density lipoprotein-cholesterol (LDL-C) levels, however, the evidence on high density lipoprotein-cholesterol (HDL-C) was insufficient. Findings didn not support antioxidative role of taurine in T2DM.

As a whole, taurine has potential to improve glycemic status and dyslipidemia. However, more clinical trials are needed to explore precise mechanisms underlying taurine on metabolic variables, oxidative stress, and inflammatory biomarkers, according to the recommendations for future directions.

The objective of this study is to test the toxicology of methanolic extract of Marrubium vulgare "MEMV" in rat and its efficiency in the treatment of systemic candidiasis.

First, forty (40) male rats "Wistar type" are used. Second, they are divided into four groups (10 rats /group) where the toxicological, microbiological and histological studies are applied. Later, the infection with 107 cells /ml of C. albicans and the curative treatment are applied by the daily administration with a gavage of 800 mg/kg of MEMV. Finally, the toxicology studies indicate that the dose of methanolic extract of Marrubium vulgare at 800 mg/kg of body weight is not harmful.

As a final result, the microbiological and histological analysis showed that the treatment with MEMV of rat colonized with 107 cells /ml of C. albicans limits the multiplication of the yeast in the intestine and colon of the colonized rat. The translocation of Candida albicans in liver, spleen and lungs in rat which is treated with 800 mg/kg after inoculation with C. albicans is significantly lower than in controls to seven post- infection days. However, we do not detect yeast in the kidneys and hearts of the infected treated groups and the infected untreated ones.

Our results suggest that MEMV limits the gastrointestinal colonization and dissemination of C.albicans in the other organs.

Epileptic seizures affect the life of noticeable number of people in all over the world. Tanacetum parthenium (TP) is used in traditional medicine. We studied the effects of hydro- ethanolic extract of TP and its n-butanol and aqueous fractions on brain oxidative damage in pentylenetetrazole (PTZ)-induced seizures in mice.

Male mice were divided into: (1) Control; (2) PTZ (100 mg/kg, i.p.); (3-5) hydro-ethanolic extract of TP (50, 100 and 200 mg/kg); (6) n-butanol (NBut) (100 mg/kg) and (7) aqueous (Aq) (100 mg/kg) fractions. Extracts were injected (i.p.) for 3 days and 30 min before PTZ. Latencies in onset of Minimal Clonic Seizures (MCS) and Generalized Tonic-Clonic Seizures (GTCS) as well as biochemical indicators were evaluated.

Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group.

Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Medium dose of TP extract and NBut fraction prolonged the MSC and GTCS latencies. Biochemical data confirmed that administration of hydro-ethanolic extract of TP significantly reduced MDA and enhanced total thiol content and the activity of SOD and CAT in brain tissues. Comparison the effect of NBut and Aq fractions with medium dose indicated a higher level of MDA and lower amount of total thiol content and the activity of SOD and CAT in brain tissues of PTZ-Aq100 and PTZ-NBut100 groups than PTZ-TP100 group.

Results demonstrated that the medium dose of TP extract had the most protective effect against brain oxidative damage in PTZ-induced seizure model. N-butanol and aqueous fractions of TP could not exert stronger effect than medium dose on reduction PTZ-induced brain oxidative stress.

Dementia is a disease in which memory, thinking, and cognitive skills are impaired, with Alzheimer’s being the most common type of dementia. Brassica nigra is useful for eliminating memory loss in traditional Persian medicine. This study aims to examine the effect of B. nigra fixed oil (BNO) on the changes in memory caused by β-amyloid.

This research was conducted on 42 Wistar rats divided into 7 groups (n=6) including 1) control (received vehicle), 2) the group receiving BNO (925 and 462.5 mg/kg), 4) sham group 5) Alzheimer group (receiving 50 ng/µl/side β-amyloid in CA1 area of hippocampus) and 2 groups receiving β-amyloid along with two different doses of BNO. The daily gavage of BNO was done 2 to 21 days post amyloid injection. The spatial memory was evaluated in Morris water maze from day 21 to 26.

The results of this study revealed that the gavage of BNO (925 mg/kg) to rats receiving β-amyloid, as compared to those receiving β-amyloid alone, significantly decreased the traveled distance and the required time for finding hidden platform on the training days and increased the time of presence in the target quadrant on the test days. The analysis of BNO with GC-MS revealed that Erucic acid (24.79%) and 11-Eicosenoic acid (17.23%) had the highest content in the BNO.

Regarding the presence of unsaturated fatty acids, it is likely that the consumption of BNO can play an important role in the prevention of memory degradation which warrants further clinical studies.

Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by chronic inflammation of the β-pancreas cells. The immunomodulatory activities related to the role of anti-inflammatory cytokines might contribute to control the inflammatory response in T1DM. This study aimed to evaluate the immunomodulatory effect of Moringa oleifera-Channa micropeltes formulation (MC) based on the profile of CD4+IL-4+, CD4+IL-10+, and CD4+TGF-β+ in type 1 diabetic mice.

A total of 30 mice were divided into six equal groups as normal, diabetic mice, diabetic mice with metformin administration, and diabetic mice with MC administration doses 1, 2 , and 3. The mice were injected intraperitoneally by 145 mg/kg BW Streptozotocin (STZ) to induce T1DM. Diabetic mice were orally administrated by MC for 14 days. The levels of CD4+IL-4+, CD4+IL-10+, and CD4+TGF-β+ were determined by flow cytometry analysis.

The DM group had low levels of IL-4 and IL-10, but high levels of TGF-β as compared to the normal. Administration of MC in certain doses significantly increased the levels of IL-4 and IL-10, while inversely decreased the levels of TGF-β in diabetic mice at the levels close to the normal and significantly different from the DM group. The glucose levels in diabetic mice after MC administration were significantly lower than the DM group.

Based on the results, MC administration in a dosage-dependent manner might have the immunomodulatory effect to reduce the inflammation by increasing IL-4 and IL-10 and suppressing TGF-β in type 1 diabetic mice.

Pentoxifylline (PTX) is a xanthine derivative with the potential cardiovascular effects. This study was done to evaluate the impact of pentoxifylline on blood pressure when added to patients’ antihypertensive regimen.

A randomized control trial were carried out on 100 patients with primary hypertension for a three-month period. The intervention group received 1200 mg daily PTX in three divided doses plus the standard treatment of antihypertensive medications, whereas the control group received only the standard treatment of hypertension. Patients’ blood pressure was measured at baseline, 4, and 12 weeks after intervention. Patients were also followed up for major adverse cardiac events.

After 4 weeks and 12 weeks of study, no significant difference was observed in systolic blood pressure (SBP) (135 ± 16 vs. 136.2 ± 17.2 mmHg, p=.72; 134.8 ± 13.3 vs. 134.3 ± 14.7 mmHg, p=.85) and diastolic blood pressure (DBP) (81.5 ± 9.9 vs. 82.4 ± 12.9 mmHg, p=.69; 80.8 ± 9 vs. 80.4 ± 10.7 mmHg, p=.84) between two groups.

The result showed that PTX has not a significant effect on BP in patients with primary hypertension.

Nephrotoxicity is one of the most important side effects of gentamicin (GEN). Accumulating evidence demonstrated the crucial roles of antioxidant compounds in the reduction of GEN-induced renal injuries. Silymarin (SM),an antioxidant agent,was demonstrated toimprove GEN-induced kidney damage. The aim of this clinical trial was to investigate the effect of SMon GEN-induced nephrotoxicity.

This randomized, double-blinded, placebo-controlled clinical trial was conducted from April 2017 to October 2019 on patients diagnosed with infectious diseases receiving GEN at least for 7 days. After approving the study and obtaining informed consents, 60 patients were included in this study. Patients in the treatment (30) and control (30) groups were given injectable GEN along with 140 mg of SM tablets or placebo orally three times a day, respectively. Demographic, laboratory, and therapeutic profilesof the patients were recorded. Urine and blood samples were collected before and on days 1, 2, 3, 5 and 7 after GEN administration and intervention.

Sex, age, GEN indication and baseline glomerular filtration rateswere found to haveno effect on GEN nephrotoxicity. SM- and placebo-treated groups exhibited no significant differencesbetweenthe indications and intervals of GEN administration. The overall rate of GEN nephrotoxicity in the SM group was significantly lower than that in the placebo group (16.7% and 53.3%, respectively; p: 0.003). In addition, the risk of GEN nephrotoxicity in patients receiving placebowas significantly higher than those receivingSM(OR:12.69, 95%, CI: 1.38-116.74; p:0.03). Serum creatininewasfound to be significantly higher in the placebo-treated group than that in theSM-treatedgroup (p<0.05). However, the frequency of acute tubular necrosis on days 2, 3, 5, and 7 after GEN administration exhibited no significant differences between SM- and placebo-treated patients.

This study demonstratedthat SM could attenuate renal injury in GEN-treated patients.

Tanshinone IIA(TA) could be used for the treatment of some diseases. However, the clinical application of TA was hindered by its poor water - solubility and low oral bioavailability, etc. The aim of this study was to improve its oral bioavailability and dissolution by encapsulating TA with hydroxypropyl–beta–cyclodextrin (HP-β-CD).

The encapsulation composite of HP-β-CD/TA was prepared through solution method with optimization of response surface test design by taking encapsulation efficiency and drug loading as the goals; the in-vitro dissolution and in-vivo metabolism of the composite in rats were evaluated.

The optimal concentration of HP-β-CD in water was 0.4 g/mL; the optimal ratio of TA to HP-β-CD was 1:7 in weight for the encapsulating process at 50°C with stirring for 2h; the encapsulation efficiency and drug loading were 84.06% and 7.38%, respectively; the cumulative release of TA from HP–β -CD TA composite in vitro dissolution reached to 72% within 90 min, which was 3.78 times of that of the original TA substance; the area under the curves of AUC(0-t) and AUC(0-∞) of the HP–β –CD -TA inclusion composite were 3.71 and 3.42 times of the original TA substance under p<0.01, respectively. The apparent distribution volume VZ/F and the clearance rate VLZ/F of HP–β –CD -TA inclusion composite decreased by 7.71 and 3.48 times as compared with the original TA substance, respectively.

The improvements of bioavailability and dissolution by encapsulating TA with HP-β-CD were effective.

Hydrochlorothiazide HCl (HCTZ) is first line medication in the management of hypertension, however its poor solubility and GI irritation warrants long term application. The aim of present study was to prepare hydrochlorothiazide HCl (HCTZ) loaded monodisperse microparticles of chitosan (CS) for sustained delivery.

In the present study chitosan microparticle were prepared using ionic gelation method. The effect of input parameters such as concentration of chitosan and pH of CS solution on the mean particle size (PS), zeta potential (ZP), polydispersity index (PDI) and in-vitro drug release were investigated. In-vitro drug release from the microparticles was studied using Franz diffusion cell. Structural formation and surface morphology was investigated using FTIR and SEM, respectively.

PS of CS microparticles ranges from 0.878±0.066 to 1.963±0.011 µm, ZP between 33.43±0.80 mV to 53.6±2.06 mV, PDI values from 0.271±0.063 to 0.842±0.073. The optimized CSMP- 3 (1.5% chitosan, pH 3) showed PS 1.672 ± 0.073 µm, ZP 53.6 ±2.06 mV, PdI 0.481±0.053, %EE 80.8±2.27% and HCTZ release of around 80% in 8 hours. FTIR reveals successful formation of crosslinked structure. SEM shows irregular surface owing preparation procedure. Drug kinetics modeled with Korsemeyer–Peppas equation revealed non-Fickian diffusion mechanism.

Drug permeation study showed more than 70% of drug permeated through membrane. In conclusion, the CS microparticles can be used for the sustained delivery of HCTZ which would reduce the dosing frequency and improved patient compliance.

Physiologically generated supersaturation and subsequent precipitation of a weakly basic drug in the small intestine leads to compromised bioavailability.

In this work, the pH -induced precipitation of dipyridamole (DPD) as a model weakly basic drug in the presence of Eudragit L100 (Eu) and hydroxypropyl cellulose (HPC) was investigated. Inhibitory effects of the polymers on precipitation of DPD at varying drug/polymer ratios were examined. The effects of the polymers on the DPD dissolution property were assessed using drug/polymer physical mixtures (PMs) and solid dispersions (SDs).

Significant inhibitory effects on precipitation were found using Eu, while HPC as well inhibited precipitation, but to a lower level than found with Eu. The PMs resulted in higher area under the dissolution curve (AUDC) compared to SDs. For SDs, the AUDC was limited by the slow release of the drug from the polymers in acidic pH which in turn decreased supersaturation of DPD following acidic to neutral pH transition.

From these results, it may be supposed that both the ability to create and stabilize supersaturation separately of each other to be important for enhancing dissolution of DPD.

A simple, fast, efficient, and environmentally friendly microextraction technique named salt induced liquid-liquid extraction combined with amine based deep eutectic solvent-dispersive liquid-liquid microextraction method followed by gas chromatography-flame ionization detector was applied for the determination of some anti-seizure drugs in urine samples.

In this method, sodium chloride (30% w/v) was dissolved in the sample solution (adjusted at pH=10) as phase separation agent and iso–propanol was added to the solution. After manually shaking, the solution was centrifuged and the supernatant phase was removed and mixed with choline chloride: benzyl ethylenediamine (85 µL) and the mixture was rapidly dispersed into a deionized water containing 5.0 % w/v, sodium chloride and adjusted at pH=10. The cloudy solution was centrifuged and the sedimented phase was removed and 1 µL of it was injected into the determination system.

Under final conditions, the limits of detection and quantification at the ranges of 3.4-6.9, and 11.5-23.3 ng mL-1 were obtained, respectively. The relative standard deviations for intra- and inter day assays were lower than 10.9%. The effect of exogenous and endogenous effect on the performance of the method was studied and the results showed that these factors were nearly effect less on the efficiency.

The introduced method was satisfactorily utilized to determinate the selected benzodiazepines drugs in the patients’ urine samples.

In the present work, an analytical method based on high performance liquid chromatography–diode array detection has been reported to evaluate the presence of some widely used pesticides in plasma samples of the farmers exposed to the pesticides in farm lands and rural zones. Prior to instrumental analysis, the analytes are extracted using a two–step extraction procedure based on a combination of cold–induced homogenous liquid–liquid extraction and dispersive liquid–liquid microextraction.

In this method, initially acetonitrile is added to a tube containing the plasma sample and the mixture is vortexed. By this action, the proteins of plasma are precipitated at the bottom of the tube after centrifugation and a homogenous solution is collected on them. Subsequently, the mixture is placed in liquid nitrogen for a few seconds to freeze the aqueous phase. As a result, the homogenous state is broken and the analytes are extracted into the supernatant organic phase (acetonitrile), which is subsequently removed and used in the following microextraction method.

Under the optimum extraction conditions, the proposed method indicated good extraction recoveries (59–80%), satisfactory repeatability (relative standard deviation ≤ 6% for intra– and inter–day precisions), and low limits of detection (1.4–2.3 μg L−1).

Finally, various plasma samples of the farmers were analyzed by the introduced method. Ease of operation, being environmentally friendly, rapidity, and low cost can be the main advantages of the introduced approach.

Venous thromboembolism (VTE) is still a problematic situation in children. Drugs like warfarin, enoxaparin, and heparin are current standard of care in childhood VTE. This study was designed to compare the efficacy of warfarin with dabigatran etexilate in children with VTE.

This randomized and active-controlled study was done in Amir-Kabir Hospital, Arak, Iran. Twenty-five children aged between 6 and 18 years with VTE were included. Study subjects were randomized 1:1 to enoxaparin 1 mg/kg twice daily and daily 0.2 mg/kg warfarin or enoxaparin 1 mg/kg twice daily and dabigatran etexilate twice daily. Enoxaparin therapy was continued for 5 days. Treatment with warfarin and dabigatran continued for 6 months. Patients were monitored for minor and major bleeding events, thrombus extension or recurrence, and death.

A total of 23 patients presented with deep-vein thrombosis completed the study and followed up over the course of 6 months. Dabigatran had similar effects to warfarin with respect to the thrombus cure, which occurred in 10 patients in the dabigatran group (90 %) and 9 patients in the warfarin group (81%). There were no differences in the frequency of bleeds, either major or minor (P > 0.05). GI upset was the most common side effects seen in both groups, and the differences were significant (P < 0.05).

Our study suggests that a 6-month treatment with dabigatran and warfarin had similar effects in secondary prevention of VTE in children < 18 yr. Dabigatran therapy was associated with more gastrointestinal upset.