Design of three-component essential oil extract mixture from Cymbopogon flexuosus, Carum carvi, and Acorus calamus with enhanced antioxidant activity.

The development of novel antioxidant compounds with high efficacy and low toxicity is of utmost importance in the medicine and food industries. Moreover, with increasing concerns about the safety of synthetic components, scientists are beginning to search for natural sources of antioxidants, especially essential oils (EOs). The combination of EOs may produce a higher scavenging profile than a single oil due to better chemical diversity in the mixture. Therefore, this exploratory study aims to assess the antioxidant activity of three EOs extracted from Cymbopogon flexuosus, Carum carvi, and Acorus calamus in individual and combined forms using the augmented-simplex design methodology. The in vitro antioxidant assays were performed using DPPH and ABTS radical scavenging approaches. The results of the Chromatography Gas-Mass spectrometry (CG-MS) characterization showed that citral (29.62%) and niral (27.32%) are the main components for C. flexuosus, while D-carvone (62.09%) and D-limonene (29.58%) are the most dominant substances in C. carvi. By contrast, ß-asarone (69.11%) was identified as the principal component of A. calamus (30.2%). The individual EO exhibits variable scavenging activities against ABTS and DPPH radicals. These effects were enhanced through the mixture of the three EOs. The optimal antioxidant formulation consisted of 20% C. flexuosus, 53% C. carvi, and 27% A. calamus for DPPHIC50. Whereas 17% C. flexuosus, 43% C. carvi, and 40% A. calamus is the best combination leading to the highest scavenging activity against ABTS radical. These findings suggest a new research avenue for EOs combinations to be developed as novel natural formulations useful in food and biopharmaceutical products.

Unveiling the volatile compounds and antibacterial mechanisms of action of Cupressus sempervirens L., against Bacillus subtilis and Pseudomonas aeruginosa.

Cupressus sempervirens is a known traditional plant used to manage various ailments, including cancer, inflammatory and infectious diseases. In this investigation, we aimed to explore the chemical profile of Cupressus sempervirens essential oil (CSEO) as well as their antibacterial mode of action. The volatile components were characterized using gas chromatography coupled to a mass spectrometer (GC-MS). The results revealed remarkable antibacterial properties of EO derived from C. sempervirens. GC-MS analysis indicated that C. sempervirens EO characterized by δ-3-carene (47.72%), D-limonene (5.44%), ß-pinene (4.36%), ß-myrcene (4.02%). The oil exhibited significant inhibitory effects against a range of bacteria, including Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 13048, Bacillus cereus (Clinical isolate), Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. These inhibitory effects surpassed those of conventional antibiotics. Furthermore, the EO demonstrated low minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs), indicating its bactericidal nature (MBC/MIC < 4.0). Time-kill kinetics analysis showed that CSEO was particularly effective at 2 × MIC doses, rapidly reduced viable count of B. subtilis and P. aeruginosa within 8 h. This suggests that the oil acts quickly and efficiently. The cell membrane permeability test further demonstrated the impact of CSEO on the relative conductivity of B. subtilis and P. aeruginosa, both at 2 × MIC concentrations. These observations suggest that EO disrupts the bacterial membrane, thereby influencing their growth and viability. Additionally, the cell membrane integrity test indicated that the addition of CSEO to bacterial cultures resulted in the significant release of proteins from the bacterial cells. This suggests that EO affects the structural integrity of the bacterial cells. Furthermore, the anti-biofilm assay confirmed the efficacy of CSEO as a potent anti-biofilm agent. It demonstrated the oil's ability to inhibit quorum sensing, a crucial mechanism for biofilm formation, and its competitive performance compared to the tested antibiotics.

Antioxidant, Volatile Compounds; Antimicrobial, Anti-Inflammatory, and Dermatoprotective Properties of Cedrus atlantica (Endl.) Manetti Ex Carriere Essential Oil: In Vitro and In Silico Investigations.

Cedrus atlantica (Endl.) Manetti ex Carriere is an endemic tree possessing valuable health benefits which has been widely used since time immemorial in international traditional pharmacopoeia. The aim of this exploratory investigation is to determine the volatile compounds of C. atlantica essential oils (CAEOs) and to examine their in vitro antimicrobial, antioxidant, anti-inflammatory, and dermatoprotective properties. In silico simulations, including molecular docking and pharmacokinetics absorption, distribution, metabolism, excretion, and toxicity (ADMET), and drug-likeness prediction were used to reveal the processes underlying in vitro biological properties. Gas chromatography-mass spectrophotometry (GC-MS) was used for the chemical screening of CAEO. The antioxidant activity of CAEO was investigated using four in vitro complementary techniques, including ABTS and DPPH radicals scavenging activity, ferric reductive power, and inhibition of lipid peroxidation (ß-carotene test). Lipoxygenase (5-LOX) inhibition and tyrosinase inhibitory assays were used for testing the anti-inflammatory and dermatoprotective properties. GC-MS analysis indicated that the main components of CAEO are ß-himachalene (28.99%), α-himachalene (14.43%), and longifolene (12.2%). An in vitro antimicrobial activity of CAEO was examined against eleven strains of Gram-positive bacteria (three strains), Gram-negative bacteria (four strains), and fungi (four strains). The results demonstrated high antibacterial and antifungal activity against ten of them (>15 mm zone of inhibition) using the disc-diffusion assay. The microdilution test showed that the lowest values of MIC and MBC were recorded with the Gram-positive bacteria in particular, which ranged from 0.0625 to 0.25 % v/v for MIC and from 0.5 to 0.125 % v/v for MBC. The MIC and MFC of the fungal strains ranged from 0.5 to 4.0% (MIC) and 0.5 to 8.0% v/v (MFC). According to the MBC/MIC and MFC/MIC ratios, CAEO has bactericidal and fungicidal activity. The results of the in vitro antioxidant assays revealed that CAEO possesses remarkable antioxidant activity. The inhibitory effects on 5-LOX and tyrosinase enzymes was also significant (p < 0.05). ADMET investigation suggests that the main compounds of CAEO possess favorable pharmacokinetic properties. These findings provide scientific validation of the traditional uses of this plant and suggest its potential application as natural drugs.

Phytochemical, Antidiabetic, Antioxidant, Antibacterial, Acute and Sub-Chronic Toxicity of Moroccan Arbutus unedo Leaves.

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

Prevalence of Undiagnosed Iron Deficiency Anemia and Associated Factors Among Female Undergraduate Medical Students in Makkah, Saudi Arabia.

INTRODUCTION: Iron deficiency anemia is the most common type of anemia according to the World Health Organization. Females are more likely to be affected than males. There are several factors causing iron deficiency anemia, such as increased loss of iron, decreased intake of iron, and increased utilization of iron. There are limited research studies evaluating the risk factors that cause anemia among female medical students in Saudi Arabia. For this, the study aimed to identify the prevalence of undiagnosed iron deficiency anemia (IDA) among young female university students and to identify if there is any correlation between IDA and several factors including dietary habits, psychological stress, anxiety status, and body mass index. MATERIALS AND METHODS: A cross-sectional observational study was performed between October 2022 and December 2022 with a sample of 100 healthy female students aged between 19 and 23 years, who were studying at the medical colleges of Umm Al-Qura University, Saudi Arabia. Blood samples were collected to perform complete blood count and iron profile tests. Also, a survey was done to find correlation between iron deficiency anemia and dietary intake, drinks, stress, anxiety, and body mass index (BMI). Independent t-test or Mann-Whitney U test were used to compare values for non-anemic with anemic participants, and linear regression tests were used to analyze differences between non-anemic and anemic participants' dietary intake factors and stress and anxiety scores. The level of significance was set at p<0.05. RESULTS: The findings represent an overall prevalence of iron deficiency anemia in female medical students based on the lab finding results. Thus, students were divided into two following groups: anemic (13%) with hemoglobin (Hb) concentration <12 g/dL and non-anemic (84%) with Hb concentration ≥12 g/dL. When comparing the two groups, results showed significant differences in the majority of RBC indices (hematocrit {HCT}, mean corpuscular volume {MCV}, mean corpuscular hemoglobin {MCH}, red cell distribution width {RDW}) and iron profiles, p-value was <0.05. On evaluation of the different types of food consumption, the mean iron intake was around 7 mg/day, and in 65% of the participants, it was below the estimated average requirement (EAR) of iron (8.1 mg/dL). The perceived stress scale (PSS) shows that 63% of the participants experienced moderate stress and 58% reported severe anxiety by the generalized anxiety disorder (GAD) scale. In multiple linear regression, iron was positively associated with hemoglobin concentrations, whereas stress scores were negatively associated with hemoglobin concentrations. CONCLUSION: There is a relatively low prevalence of anemia and most of it was found of the microcytic type, indicating that this condition is a common health issue among local female college students. There was no independent association between stress or anxiety and hemoglobin levels.

Combination of Panax ginseng C. A. Mey and Febuxostat Boasted Cardioprotective Effects Against Doxorubicin-Induced Acute Cardiotoxicity in Rats.

Doxorubicin (DOX) is an anticancer agent for treating solid and soft tissue malignancies. However, the clinical use of DOX is restricted by cumulative, dose-dependent cardiotoxicity. Therefore, the present study aimed to assess the cardioprotective effects of P. ginseng C. A. Mey, febuxostat, and their combination against DOX-induced cardiotoxicity. Thirty-five Sprague Dawley male rats were used in this study. The animals were randomly divided into five groups, with seven rats per group. The control group received normal saline, the induced group received DOX only, and the treated group received P. ginseng, febuxostat, and their combination before DOX treatment. Biomarkers of acute cardiac toxicity were assessed in each group. Results showed that treatment with the combination of febuxostat and P. ginseng before DOX led to a significant improvement in the biomarkers of acute DOX-induced cardiotoxicity. In conclusion, the combination of P. ginseng and febuxostat produced more significant cardioprotective effects against DOX-induced cardiotoxicity when compared to either P. ginseng or febuxostat when used alone. The potential mechanism of this combination was mainly mediated by the anti-inflammatory and antioxidant effects of P. ginseng and febuxostat.

Enhanced renoprotective actions of Paricalcitol and omega-3 fatty acids co-therapy against diabetic nephropathy in rat.

Introduction: Although the synthetic vitamin D analogue, Paricalcitol, and omega-3 Fatty acids (ω-3) alleviated diabetic nephropathy (DN), their combination was not previously explored. Objectives: This study measured the potential ameliorative effects of single and dual therapies of Paricalcitol and/or ω-3 against DN. Methods: Forty rats were assigned as follow: negative (NC) and positive (PC) controls, Paricalcitol, ω-3 and Paricalcitol + ω-3 groups. Diabetes was generated by high-fat/high-fructose diet and a single streptozotocin injection (40 mg/kg). DN was confirmed by raised fasting blood glucose (FBG), polyuria, proteinuria, and decreased urine creatinine levels. Paricalcitol intraperitoneal injections (0.25 µg/Kg/day; 5 times/week) and oral ω-3 (415 mg/kg/day; 5 times/week) started at week-9 and for eight weeks. Results: The PC group showed hyperglycaemia, dyslipidaemia, abnormal renal biochemical parameters, elevated caspase-3 expression, and increased apoptosis by TUNEL technique. The mRNAs and proteins of the pathogenic molecules (TGF-ß1/iNOS) and markers of tissue damage (NGAL/KIM-1) augmented substantially in the PC renal tissues relative to the NC group. The oxidative stress (MDA/H2O2/protein carbonyl groups) and pro-inflammatory (IL1ß/IL6/TNF-α) markers increased, whereas the anti-inflammatory (IL10) and anti-oxidative (GSH/GPx1/GR/SOD1/CAT) declined, in the PC renal tissues. The monotherapy groups were associated with ameliorated FBG, lipid profile and renal functions, and diminished TGF-ß1/iNOS/NGAL/KIM-1/Caspase-3 alongside the apoptotic index than the PC group. The oxidative stress and pro-inflammatory markers decreased, whilst the anti-oxidative and anti-inflammatory molecules escalated, in the monotherapy groups than the PC group. Although the Paricalcitol renoprotective actions were better than ω-3, all the biomarkers were abnormal than the NC group. Alternatively, the Paricalcitol + ω-3 protocol exhibited the best improvements in metabolic control, renal functions, oxidative stress, inflammation, and apoptosis. However, FBG and tissue damage were persistently higher in the co-therapy group than controls. Conclusions: Both monotherapies showed modest efficacy against DN, whereas their combination displayed boosted renoprotection, possibly by enhancing renal anti-oxidant and anti-inflammatory pathways.

Clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture: A multicenter study.

Background and aim: Indeterminate biliary stricture (IBS) is a frequently encountered clinical problem. In this study, we aimed to highlight the clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture. Method: A Retrospective multicenter study included all patients diagnosed with IBS in the participating centers between 2017 and 2021. Data regarding IBS such as presentations, patient characteristics, diagnostic and therapeutic modalities were collected from the patients' records and then were analyzed. Results: Data of 315 patients with IBS were retrospectively collected from 7 medical centers with mean age: 62.6 ± 11 years, females: 40.3% and smokers: 44.8%. For diagnosing stricture; Magnetic resonance imaging/Magnetic resonance cholangiopancreatography (MRI/MRCP) was the most frequently requested imaging modality in all patients, Contrast enhanced computerized tomography (CECT) in 85% and endoscopic ultrasound (EUS) in 23.8%. Tissue diagnosis of cholangiocarcinoma was achieved in 14% only. The used therapeutic modalities were endoscopic retrograde cholangiopancreatography (ERCP)/stenting in 70.5%, percutaneous trans-hepatic biliary drainage (PTD): 17.8%, EUS guided drainage: 0.3%, and surgical resection in 8%. The most frequent type of strictures was distal stricture in 181 patients, perihilar in 128 and intrahepatic in 6. Distal strictures had significant male predominance, with higher role for EUS for diagnosis and higher role for ERCP/stenting for drainage, while in the perihilar strictures, there was higher role for CECT and MRI/MRCP for diagnosis and more frequent use of PTD for drainage. Conclusion: Indeterminate biliary stricture is a challenging clinical problem with lack of tissue diagnosis in most of cases mandates an urgent consensus diagnostic and treatment guidelines.

Polymer-Templated Durable and Hydrophobic Nanostructures for Hydrogen Gas Sensing Applications.

A simple and hands-on one-step process has been implemented to fabricate polymer-templated hydrophobic nanostructures as hydrogen gas sensing platforms. Topographic measurements have confirmed irregular hills and dips of various dimensions that are responsible for creating air bubble pockets that satisfy the Cassie-Baxter state of hydrophobicity. High-resolution field-emission scanning electron microscopy (FESEM) has revealed double-layer structures consisting of fine microscopic flower-like structures of nanoscale petals on the top of base nanostructures. Wetting contact angle (WCA) measurements further revealed the contact angle to be ~142.0° ± 10.0°. Such hydrophobic nanostructures were expected to provide a platform for gas-sensing materials of a higher surface area. From this direction, a very thin layer of palladium, ca. 100 nm of thickness, was sputtered. Thereafter, further topographic and WCA measurements were carried out. FESEM micrographs revealed that microscopic flower-like structures of nanoscale petals remained intact. A sessile drop test reconfirmed a WCA of as high as ~130.0° ± 10.0°. Due to the inherent features of hydrophobic nanostructures, a wider surface area was expected that can be useful for higher target gas adsorption sites. In this context, a customized sensing facility was set up, and H2 gas sensing performance was carried out. The surface nanostructures were found to be very stable and durable over the course of a year and beyond. A polymer-based hydrophobic gas-sensing platform as investigated in this study will play a dual role in hydrophobicity as well as superior gas-sensing characteristics.

Upward Migration and Coiling of the Distal Catheter Toward the Valve Site.

Hydrocephalus, which is caused by the accumulation of cerebrospinal fluid (CSF), is a common condition in children. It is known to be most likely treated by the insertion of a ventriculoperitoneal (VP) shunt. However, a VP shunt can lead to multiple complications. The upward migration of a VP shunt is considered rare. A newborn male baby with a known case of Chiari malformation type 2 associated with myelomeningocele (MMC) and hydrocephalus had a VP shunt inserted for control of the hydrocephalus. He presented two months after the surgery with occipital swelling at the surgical site. Shunt series followed by Computerized tomography (CT) scan showed that the distal end of the catheter had migrated upward and coiled around the valve. Urgent revision of the VP shunt was performed. Reabsorption of subgaleal fluid, increased abdominal pressure, repeated abdominal wall contraction, and repeated head motion of the child are the previously suggested theories of upward migration of distal catheter to the site of the valve. However, the combination of multiple theories can be the logical explanation, as they do not oppose each other.

Antioxidant Activity Derived from Marine Green-Lipped Mussel Perna canaliculus Extracts in Mice.

This study investigates the antioxidant activities of lipid, protein, and carbohydrate extracts from the marine mollusk Perna canaliculus. Lipids were extracted using acetone, which was followed by protein extraction using the broad-spectrum enzyme Alcalase and then carbohydrate extraction using cetylpyridinium chloride. Eighty white BALB/c mice were divided into eight groups according to the administered extracts. Groups 1 and 5 were the control and toxin control groups, respectively. Groups 2, 3, and 4 were administered lipid, protein, and carbohydrate extracts, respectively. The other groups were administered P. canaliculus extracts as well as gentamicin and acetaminophen, known as ethanolic extracts, derived from Nerium oleander to induce oxidation stress. All groups showed significant improvements in body weight (p < 0.05). The lipid extract group showed a significant decrease in low-density lipoprotein cholesterol (p < 0.05) and a significant increase in high-density lipoprotein cholesterol (p < 0.05). After the toxin injection, all groups treated with P. canaliculus extracts showed increased antioxidant effects on hepatocytes (p < 0.05). The lipid extracts induced antioxidant effects to protect the kidney by increasing lipid peroxidation (p < 0.05) and catalase activities (p < 0.05). Also, protein extracts showed antioxidant effects by increasing glutathione and catalase levels significantly (p < 0.005). In conclusion, P. canaliculus extracts, especially lipids and proteins, have potent antioxidant activities that protect vital organs from oxidation stress.

Antioxidant and antithrombotic effects of green mussels (Perna canaliculus) in rats.

In the past decade, the use of marine mussels as seafood is being more popular. They considered being a rich source of various nutritional bioactive compounds that aroused the scientific community's interest. This study investigated the antioxidant and the antithrombotic consequences on Sprague-Dawley male rats after adding dried New Zealand mussel Perna canaliculus in their diet. The biochemical, hematological and histopathological changes were also observed. Forty rats were divided into four groups according to the amount of dried mussels in their diet, in addition to a control group that consumed a basal diet only. Group 1 consumed 25% dried mussels in its basal diet; Group 2 consumed 35% dried mussels in its basal diet, and Group 3 was consumed 45% dried mussels in its basal diet. The biochemical parameters showed improvements in liver function. Interestingly, the lipid profile decreased, especially the low-density lipoprotein cholesterol (LDL-C) levels which were reduced significantly in Group 3 (p < .01). These observations were accompanied by a decrease in iron levels significantly as the amount of dried mussels increased (p < .01). Furthermore, the noticed changes in the hematological profile prove that there is an increase in antithrombotic activity. Dried mussels had potent antioxidant effects in the liver as shown by increased lipid peroxide (p < .05), reduced glutathione (p < .05), and glutathione peroxidase (GSH-Px; p < .05). Additionally, antioxidant activity in the kidney was shown to increase through GSH-Px activity (p < .01). In conclusion, these results indicate that consuming dried mussels resulted in improved biochemical and antioxidants activities and could be used as an antithrombotic agent.

Polycyclic Aromatic Hydrocarbon Levels in Wistar Rats Exposed to Ambient Air of Port Harcourt, Nigeria: An Indicator for Tissue Toxicity.

This study investigated the PAH levels in Wistar rats exposed to ambient air of the Port Harcourt metropolis. Twenty Wistar rats imported from a nonpolluted city (Enugu) were exposed to both indoor and outdoor air. Following the IACUC regulation, baseline data were obtained from 4 randomly selected rats, while the remaining 16 rats (8 each for indoor and outdoor) were left till day 90. Blood samples were obtained by cardiac puncture, and the PAH levels were determined using Gas Chromatography Flame-Ionization Detector (GC-FID). GraphPad Prism (version 8.0.2) Sidak's (for multiple data set) and unpaired t-tests (for two data sets) were used to evaluate the differences in group means. Seven of the PAHs found in indoor and outdoor rats were absent in baseline rats. The mean concentrations of PAH in indoor and outdoor animals were higher than those of baseline animals, except for Benzo(a)pyrene, which was found in baseline animals but absent in other animal groups. Additionally, Dibenz(a,h)anthracene, Indeno(1,2,3-c,d)pyrene, Pyrene, 2-methyl, and other carcinogenic PAHs were all significantly higher (p < 0.05) in outdoor groups. The vulnerable groups in Port Harcourt are at the greatest risk of such pollution. Therefore, urgent environmental and public health measures are necessary to mitigate the looming danger.

Substance Use, Highly Active Antiretroviral Therapy, and Liver Enzymes: Evidence From a Cross-Sectional Study of HIV-Infected Adult Patients Without Comorbidities on HAART in the University of Port Harcourt Teaching Hospital.

This study applied a structural equation modeling (SEM) to evaluate the role of substance use (alcohol, smoking, and trado-medicine use) to changes in the liver enzymes (AST, ALT, and ALP) levels in HIV-infected adult patients on a highly active antiretroviral treatment (HAART) for not <1 year. The study was a cross-sectional, part of a randomized comparative trial (Ref: UPH/CEREMAD/REC/19), involving 129 (46 males and 83 females) HIV-infected adult patients. Liver enzyme levels were determined from analyzed blood samples using the Clinical Chemistry Analyser (VS10) manufactured by Vitro Scient, while the study determined substance use using a reliable (Cronbach alpha = 0.805) rapid-exploratory survey questionnaire. Liver enzyme values were further categorized into: normal or abnormal using normal reference ranges (ALT = 7-55 U/L, AST = 8-48 U/L, and ALP = 40-129 U/L). STATGRAPHICS V16.1.11 (StatPoint Tech., Inc.) and SPSS (IBM® Amos V21.0.0, USA) were used to analyze the data. Among the HIV-HAART patients, 27.9% were alcohol users, 20.9% smokers, and 20.1% trado-medicine users. In addition, ALP (71.3%) abnormality was higher than ALT (34.9%) and AST (28.7%). The result from the SEM provided only a partial support for our hypotheses of direct substance use effects on the liver enzyme levels and abnormalities; with a direct association of alcohol with an elevated AST (b = 0.170, p = 0.05) and smoking with a higher AST (b = 0.484, p < 0.01) and ALT (b = 0.423, p < 0.01) values. Trado-medicine use was not directly associated with enzyme elevation and abnormality. In conclusion, ALP abnormality was the most common, and there is a close association between an elevated ALT and AST, with or without an elevated ALP. The study found that HIV-HAART patients who drink or smoke will have at least one or more abnormal transaminases. The possible explanation to the increased risk among HIV-HAART patients could be associated with the metabolic pressures and supra-additive effects on the livers.

Gemcitabine induced cytotoxicity, DNA damage and hepatic injury in laboratory mice.

The present study was conducted to demonstrate cytotoxicity, apoptosis and hepatic damage induced by gemcitabine in laboratory mice. Animals were treated with a single dose of gemcitabine (415 mg/kg body wt), equivalent to a human therapeutic dose, and sacrificed after 1, 2 and 3 weeks. A significant decrease in mean body weight and absolute liver weight was registered. The levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased as a result of this induced stress. Various structural changes were observed in the liver tissue of treated mice, as evident in the histological sections. Specifically, gemcitabine exposure was able to induce apoptosis in liver cells, and the incidence of TUNEL positive liver cells was increased compared to the control group. DNA fragmentation appeared on agarose gel and flow cytometry analysis confirmed the induction of apoptosis. These findings in gemcitabine-treated animal tissues suggest that inhibition or disruption of cells' DNA synthesis may be the mechanism by which this drug induces toxicity in the animal body.

The remedial effect of Thymus vulgaris extract against lead toxicity-induced oxidative stress, hepatorenal damage, immunosuppression, and hematological disorders in rats.

The Thymus vulgaris (T. vulgaris) has been used in foods for the flavor, aroma, and preservation and in folk medicines. The objective of the present work was to determine the antioxidant and protective effects of T. vulgaris extract against lead (Pb)-intoxicated rats. A thirty-two male Sprague-Dawley were randomly assigned into 4 equal groups and treated for six weeks as follows: group I (GP-I), served as negative control; GP-II, -III, and -IV received either Pb acetate in drinking water (500 mg/L), T. vulgaris extract (500 mg/kg/day) by oral gavage or Pb acetate with T. vulgaris extract, respectively. Blood samples were collected at the end of the study week 6 to measure the hepatic and renal biochemical markers, complete blood count alongside the serum levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis (TNF)-α, and interferon (IFN)-γ. Additionally, liver and kidney tissue specimens were collected for histopathology as well as to measure the antioxidant-reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) alongside the lipid peroxidation marker, malonaldehyde (MDA). The results indicated that Pb toxicity increased the serum levels of IL-1ß, IL-6, and TNF-α, whereas IL-10 and IFN-γ were reduced. The results showed disturbed liver and renal functions; increased serum levels of ALT, AST, ALP, total bilirubin, creatinine, and urea; and decreased total protein, albumin, and calcium. The GSH, Gpx, and CAT levels were significantly decreased in the Pb-administrated group, while MDA was increased. However, regarding the hepatorenal markers, those animals treated with T. vulgaris alone did not induce any significant changes. Moreover, the combined treatment with T. vulgaris extract together with Pb showed significant improvement in Pb-induced toxicity in all the tested parameters compared to the negative control group. We investigated the potential protective effects of the medicinal plant T. vulgaris in vivo, since there are no publications that address the potential protective effect of this leaf extract against Pb-induced hepatorenal toxicity. Our studies concluded that the T. vulgaris extract reduces Pb overload in hepatorenal tissues, and that this has a potential immunomodulatory role, antioxidant activity, and a protective effect against Pb toxicity.

Synthesis and evaluation of the affinity toward mu-opioid receptors of atypical, lipophilic ligands based on the sequence c[-Tyr-Pro-Trp-Phe-Gly-].

An ultimate and general model describing the interaction between opioid ligands and mu-opioid receptors is not available yet, so the mode of action of atypical peptide analogues or peptidomimetics is worthy of investigation. In this context, the peptide c[-Tyr-d-Pro-d-Trp-Phe-Gly-] was observed to act as an agonist toward mu-opioid receptors with appreciable potency, albeit deprived of a protonable nitrogen. This compound was synthesized as a member of a library of diastereo- or enantiomeric cyclic peptides based on the sequence of endomorphin-1, aiming to obtain lipophilic peptide ligands active at the mu-opioid receptors, having good performances in terms of resistance to enzymatic degradation and permeation of biological barriers.

Endomorphin-1 analogues containing beta-proline are mu-opioid receptor agonists and display enhanced enzymatic hydrolysis resistance.

In this paper we describe the synthesis and affinity toward the mu-opioid receptor of some tetrapeptides obtained from endomorphin-1, H-Tyr-Pro-Trp-Phe-NH(2) (1), by substituting each amino acid in turn with its homologue. The ability to bind mu-opioid receptors depends on the beta-amino acid, and in particular 4, which contains beta-L-Pro, has a K(I) in the nanomolar range. The peptides 4 and 5 are significantly more resistant to enzymatic hydrolysis than 1. The same compounds, as well as the mu-opioid receptor agonist DAMGO, produced a concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation, thus behaving as mu-opioid agonists. These features suggest that this novel class of endomorphin-1 analogues may represent suitable candidates for the in vivo investigation as potential mu-opioid receptor agonists.