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Diabetes mellitus (DM) is one of the most challenging diseases among all the other diseases in the recent era, and it is a life-threatening disorder. The best enzymes to target for treating DM are α-glucosidase and α-amylase. For this purpose, we explored numerous succinimides with ketone functionalities. First, we explored these compounds for their in vitro analysis. Compounds 1 and 4 exhibited excellent inhibition of both enzymes in in vitro studies. These compounds displayed excellent activity with IC50 values of 3.69 and 1.526 µg·mL−1 against the α-glucosidase enzyme. In the α-amylase inhibitory assay, compound 1 has shown excellent potential with an IC50 value of 1.07 µg·mL−1 and compound 4 with an IC50 value of 0.115 µg·mL−1. Based on the in vitro analysis, the potent compounds were further subjected to their in vivo analysis. Before the in vivo analysis, the toxicity profile was checked, and it was confirmed that the compounds were safe at 1,500 µg·kg−1. Then, these compounds were subjected for their in vivo anti-diabetic potential in a mouse model of diabetes. Various concentrations of compounds 1 and 4 were explored by in vivo analysis using glibenclamide as a standard drug. The blood glucose level of the tested and control groups was measured at 0 to 15 days accordingly. Similarly, we also explored compounds 1 and 4 for the oral glucose tolerance test at 0–120 min using glibenclamide as the standard drug. Hence, the succinimide having ketone moiety displayed excellent potential against diabetes.

Background The peripartum period is both a highly vulnerable stage and a significant indicator of a population’s health status. Interest is increasing in human T-cell lymphotropic virus type-1 (HTLV-1) transmission due to its adverse health impacts. However, nationally representative data on HTLV-1 that are important for health planning are unavailable for this subpopulation. Purpose This study aimed to conduct a pooled estimate of HTLV-1 prevalence among pregnant women in Nigeria to quantify its clinical burden and public health implications. Methods This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement. Results After a systematic review of the Nigerian literature, 12 studies (2,821 pregnant or postnatal women) were included in the final evidence synthesis. The estimated HTLV-1 prevalence in Nigerian peripartum women following a positive screening test by enzyme-linked immunosorbent assay was 5.44% (95% confidence interval [CI], 3.16%–9.20%). A subgroup analysis of the 2 major regions showed a slightly higher prevalence in the Western versus Southern region (5.55% [95% CI, 2.49%–11.87%]; and 4.91% [95% CI, 2.11%–11.02%]; P=0.84). However, a subgroup analysis by geopolitical zone revealed that Southwestern and Northwestern Nigeria had the highest prevalence (9.23% [95% CI, 4.35%–18.55%; I2=93%] and 7.15% [95% CI, 1.54%–27.54%]; I2=92%). Our decade-old subgroup analysis found inconsistencies in the HTLV-1 prevalence. Furthermore, our literature review revealed a prevalence of HTLV infection among patients with various clinical types of lymphomas/leukemias and myelopathy of 2%–22%. Conclusion These findings have important implications in defining the epidemiological patterns of HTLV-1 infection in Nigeria. They also suggest the presence of HTLV-endemic clusters near low-endemic areas, even within the same geopolitical zones.

OBJECTIVE: Obesity was induced in rats by feeding on a high fat diet (HFD), 60% w/w cholesterol, 20% w/w carbohydrates, and 20% w/w proteins for two months. MATERIALS AND METHODS: Animals were fed on a HFD and treated concurrently with a single daily dose of vehicle or TPPU (2 mg/kg p.o) for two months. Body weights, blood pressure, and biochemical investigations of all animals were registered at 0, 1, and 2 months of the experimental period. RESULTS: Vehicle-treated rats fed on a HFD had a considerable increase in body weight compared to age-matched control animals fed on a regular diet (regular diet; 311.40 ±9.60 vs. HFD; 446 ± 12.67). The body weight of rats fed on a HFD and concurrently treated with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4yl) urea (TPPU; 2 mg/kg p.o) daily for two months was significantly decreased (p<0.01). A significant (p<0.01) increase in the systolic blood pressure of animals and vascular dysfunction with blunted relaxant response to acetylcholine and sodium nitroprusside was evident in vehicle-treated animals fed on a HFD compared to control rats fed on a regular diet. These HFD-induced disorders were markedly attenuated in animals fed on a HFD and treated concurrently with a single daily dose of TPPU (2 mg/kg p.o). HFD diet-induced deleterious metabolic changes were prevented with concurrent administration of TPPU (2 mg/kg p.o). TPPU treatment decreased the HDF-induced increase in plasma creatinine levels (p<0.001) in rats. The adiponectin levels were decreased (p<0.001) in vehicle-treated rats fed on HFD for two months compared to control rats fed on a normal diet (p<0.001). Adiponectin levels were significantly (p<0.001) increased in rats fed on HFD and treated concurrently with TPPU (2 mg/kg p.o). HFD diet caused a marked increase in plasma leptin levels of animals which were significantly decreased in animals fed on a HFD and treated concurrently with TPPU for two months. Obese animals exhibited increased levels of plasma insulin compared to control animals fed on a regular diet which were significantly suppressed (p<0.001) by TPPU treatment. In the current investigation, TPPU treatment had a favorable impact on the levels of other metabolic parameters such as plasma cholesterol, triglycerides (TGs), low density lipoproteins (LDLs), and high density lipoproteins (HDL). HFD caused a profound increase in the serum liver enzymes, the effect was reversed by treatment of animals with TPPU (2 mg/kg p.o). CONCLUSIONS: The findings of our current study indicate the promising therapeutic potential of TPPU as a new drug candidate to manage obesity-induced cardiovascular and metabolic disorders. Soluble epoxide hydrolase inhibitors such as TPPU could prevent HFD-induced obesity and related cardiovascular and metabolic complications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease has caused a worldwide challenging and threatening pandemic (COVID-19), with huge health and economic losses. The US Food and Drug Administration, (FDA) has granted emergency use authorization for treatment with the Pfizer/BioNTech and Moderna COVID-19 vaccines. Many people have a history of a significant allergic reaction to a specific food, medicine, or vaccine; hence, people all over the world have great concerns about these two authorized vaccines. This article compares the pharmacology, indications, contraindications, and adverse effects of the Pfizer/BioNTech and Moderna vaccines. MATERIALS AND METHODS: The required documents and information were collected from the relevant databases, including Web of Science (Clarivate Analytics), PubMed, EMBASE, World Health Organization (WHO), Food and Drug Authorities (FDA) USA, Local Ministries, Health Institutes, and Google Scholar. The key terms used were: Coronavirus, SARS-COV-2, COVID-19 pandemic, vaccines, Pfizer/BioNTech vaccine, Moderna vaccine, pharmacology, benefits, allergic responses, indications, contraindications, and adverse effects. The descriptive information was recorded, and we eventually included 12 documents including research articles, clinical trials, and websites to record the required information. RESULTS: Based on the currently available literature, both vaccines are beneficial to provide immunity against SARS-CoV-2 infection. Pfizer/BioNTech Vaccine has been recommended to people 16 years of age and older, with a dose of 30 µg (0.3 m) at a cost of $19.50. It provides immunogenicity for at least 119 days after the first vaccination and is 95% effective in preventing the SARS-COV-2 infection. However, Moderna Vaccine has been recommended to people 18 years of age and older, with a dose of 50 µg (0.5 mL) at a cost of $32-37. It provides immunogenicity for at least 119 days after the first vaccination and is 94.5% effective in preventing the SARS-CoV-2 infection. However, some associated allergic symptoms have been reported for both vaccines. The COVID-19 vaccines can cause mild adverse effects after the first or second doses, including pain, redness or swelling at the site of vaccine shot, fever, fatigue, headache, muscle pain, nausea, vomiting, itching, chills, and joint pain, and can also rarely cause anaphylactic shock. The occurrence of adverse effects is reported to be lower in the Pfizer/BioNTech vaccine compared to the Moderna vaccine; however, the Moderna vaccine compared to the Pfizer vaccine is easier to transport and store because it is less temperature sensitive. CONCLUSIONS: The FDA has granted emergency use authorization for the Pfizer/BioNTech and Moderna COVID-19 vaccines. These vaccines can protect recipients from a SARS-CoV-2 infection by formation of antibodies and provide immunity against a SARS-CoV-2 infection. Both vaccines can cause various adverse effects, but these reactions are reported to be less frequent in the Pfizer/BioNTech vaccine compared to the Moderna COVID-19 vaccine; however, the Moderna vaccine compared to the Pfizer vaccine is easier to transport and store because it is less temperature sensitive. [ABSTRACT FROM AUTHOR]

Stabilization of epoxyeicosatrienoic acids (EETs) levels via soluble epoxide hydrolase (sEH) deletion or its pharmacological inhibition have been shown to have beneficial effects on inflammation, ischemia, hypertension and diabetes. Owing to the diverse role of EETs, current study was designed to evaluate the therapeutic potential of 1- trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl) urea (TPPU), a novel sEHI against fructose-induced diabetes and related complications in rats. Sprague-Dawley rats (200 -- 230 g) were divided into four different groups, each containing 10 animals. One group served as a normal control and received standard diet and drinking water. The second group served as a diseased control and received standard diet, 25% fructose in drinking water and was treated with vehicle only. The third and fourth groups received standard diet, 25% fructose in drinking water and TPPU (2 mg/kg) or metformin (150 mg/kg), respectively. All treatments were given orally for 12 weeks. At the end of the study, blood samples were collected to measure serum insulin levels and other biochemical parameters. Animals were dissected to collect tissue specimens for histological and immunohistochemistry analysis. Animals fed on fructose and treated with vehicle demonstrated elevated blood insulin and glucose levels as well as high levels (P < 0.001) of triglycerides (TGs), cholesterol, low-density lipoprotein (LDL) and homeostatic model assessment of insulin resistance (HOMA-IR) compared to naive rats. Similarly, the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), urea and uric acid were significantly (P < 0.001) increased in vehicle treated fructose fed animals. TPPU (2 mg/kg p.o.) and simultaneously fed on fructose for 12 weeks substantially decreased HOMA-IR levels, lowered blood glucose, serum cholesterol, LDLs and TGs) while high-density lipoproteins (HDL) levels were increased compared to untreated animals. Metformin, a standard reference drug showed similar results. Microscopic studies of liver and pancreatic sections of TPPU treated animals showed marked improvement in cellular architecture compared to untreated animals. Current study demonstrated profound therapeutic potential of TPPU against fructose induced-diabetes and related metabolic complications which was evident by its attenuating effect fructose-induced hyperglycemia, hyperlipidemia and impaired renal and hepatic serum markers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study evaluated the efficacy of the soluble epoxide hydrolase (sEH) inhibitor, TPPU on chronic NG-Nitro L-arginine methyl ester (L-NAME)-induced hypertension in rats and its effects on plasma Angiotensin II (Ang II), cardiac Angiotensin-converting enzyme (ACE) and Angiotensin II receptor type 1 (AT1R) expressions. MATERIALS AND METHODS: Forty Sprague Dawley rats were divided into 5 groups. Two groups served as control and received orally either vehicle or TPPU (3 mg/kg) for five weeks. The other three groups were given L-NAME (50 mg/kg/day) in drinking water for five weeks. Two weeks after the L-NAME treatment, animals received orally either saline or TPPU (3 mg/kg/day) or lisinopril (10 mg/kg/day) daily for 3 weeks. Blood pressure (BP) was measured weekly. At the end of the experiment, plasma Ang II, cardiac ACE and AT1R protein and gene expressions were determined. RESULTS: L-NAME caused a significant increase in BP of the animals. TPPU and lisinopril resulted in normalization of L-NAME-induced hypertension. They also caused a significant reduction in Ang II and ACE protein and gene expressions compared to L-NAME and vehicle-treated animals. CONCLUSIONS: This study demonstrates that TPPU effectively lowers L-NAME-induced hypertension in rats. The mechanism of its antihypertensive effect is likely mediated by the suppression of ACE gene and protein expression, leading to a lower Ang II level. [ABSTRACT FROM AUTHOR]

The genetic underpinnings of recessively inherited moderate to severe sensorineural hearing loss are not well understood, despite its higher prevalence in comparison to profound deafness. We recruited 92 consanguineous families segregating stable or progressive, recessively inherited moderate or severe hearing loss. We utilized homozygosity mapping, Sanger sequencing, targeted capture of known deafness genes with massively parallel sequencing and whole exome sequencing to identify the molecular basis of hearing loss in these families. Variants of the known deafness genes were found in 69% of the participating families with the SLC26A4, GJB2, MYO15A, TMC1, TMPRSS3, OTOF, MYO7A and CLDN14 genes together accounting for hearing loss in 54% of the families. We identified 20 reported and 21 novel variants in 21 known deafness genes; 16 of the 20 reported variants, previously associated with stable, profound deafness were associated with moderate to severe or progressive hearing loss in our families. These data point to a prominent role for genetic background, environmental factors or both as modifiers of human hearing loss severity. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Research in pharmacological science is vital to support the health needs of human beings. Measuring the research output provides information that forms the basis of strategic decisions. This study aimed to investigate the impact of Gross Domestic Product (GDP), spending on Research and Development (R&D), number of universities and scientific journals on research documents (papers), citable documents, citations per document and H-index in pharmacological science among Middle East countries. MATERIALS AND METHODS: All the 16 Middle East countries were included in the study. The information regarding GDP, spending on R&D, total number of universities and indexed scientific journals were collected. We recorded the total number of research documents, citable documents, citations per document and H-index in pharmacological science during the period 1996-2011. The main sources for information were World Bank, Web of Science, Journal Citation Reports (Thomson Reuters) and SCI-mago/Scopus. RESULTS: The mean per capita GDP of all the Middle East countries is 18125.49±5386.28 US$, spending on R&D 0.63±0.28% of GDP in US$, number of universities 36.56±11.33 and mean ISI indexed journal are 8.25±3.93. The number of re- search documents published in pharmacological science among the Middle East countries during the period 1996-2011 is 1344.44±499.34; citable documents 1286.37±476.34; citations per document 7.62± 0.84; and H-index is 30.68±6.32.There was a positive correlation between spending on R&D and citations per documents (r = 0.56, p = 0.02), H-Index (r = 0.56, p = 0.02); number of universities and research documents (r = 0.72, p = 0.002), citable documents (r = 0.72, p = 0.001); ISI indexed journals and research documents (r = 0.88, p = 0.0001), citable documents (r = 0.88, p = 0.0001), H-Index (r = 0.67, p = 0.004). However, there was no correlation between the GDP per capita and research outcome in pharmacological science. CONCLUSIONS: There is a positive association between spending on R&D, number of universities and indexed scientific journals on research out-come in pharmacological science in Middle East. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Hypericum (H.) perforatum, popularly called St. John's Wort has been used traditionally for the treatment of anxiety, depression and as a nerve tonic. Large amount of clinical and animal experimental data demonstrate that H. perforatum acts by biochemical mechanisms similar to the tricyclic antidepressants or serotonin reuptake inhibitors. However, its efficacy in comparison to standard antidepressant drugs is not well studied. The present study evaluated H. perfortum extract in animal models of depression compared to clinically used antidepressants. MATERIALS AND METHODS: The effects of standardized extract of H. perforatum was compared with standard antidepressants using animal models of depression such as forced swim test (FST), yohimbine induced lethality test, pnetylenetetrazole (PTZ) induced convulsion and locomotor activity tests. Different doses of the plant extract and standard drugs were administered to rats or mice intraperitoneally (i.p). RESULTS: In the FST, H. perforatum extract (30-90 mg/kg i.p.) caused a dose dependent reduction in immobility time in rats with maximal effect being 53% at 90 mg/kg. This effect was reversed at higher doses (100 mg/kg) showing a U-shaped dose response curve. Fluoxetine and imipramine (30-70 mg/kg i.p.) produced similar reduction in the immobility time in rats. Venlafaxine exhibited weak antidepressant effect. H. perforatum extract (30-100 mg/kg i.p.), dothiepin (10-50 mg/kg i.p.), fluoxetine (30-60 mg/kg i.p.) and venlafaxine (20- 40 mg/kg i.p.) potentiated yohimbine induced lethality. PTZ induced toxicity was also enhanced with these agents. In the locomotor activity test H. perforatum decreased the locomotor counts of mice similar to standard antidepressants. CONCLUSIONS: H. perforatum has antidepressant properties similar to standard antidepressants. The antidepressant profile of H. perforatum is closely related to the selective serotonin reuptake inhibitors class of antidepressants. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: The current investigation was carried out to explore the pharmacological basis of the crude extract of Conyza bonariensis (Cb.Cr) for its use in constipation and diarrhea. MATERIALS AND METHODS: The plant extract of Conyza bonariensis (C. bonariensis) was prepared, isolated guinea-pig ileum and rabbit jejunum preparations were used to evaluate its gut modulator effects. RESULTS: The Cb.Cr (0.3-10 mg/mL) exhibited spasmogenic effect in isolated guinea-pig ileum preparation, which was about 19-84% of the acetylcholine maximum. Pretreatment of the tissues with atropine (0.1 μM) abolished the contractile effect, similar to acetylcholine. Among the fractions, only the butanol fraction exhibited atropine sensitive contractile effect. In isolated rabbit jejunum preparations, Cb.Cr produced appreciable atropine-sensitive spasmogenic effect at lower concentrations (0.03-0.3 mg/mL) followed by spasmolytic effect at next higher concentration (1.0 and 3.0 mg/mL). Cb.Cr caused an inhibition of the high K+ induced contraction in isolated rabbit jejunum preparation with EC50 value of 0.62 mg/mL. Similarly, verapamil, a standard calcium blocker, inhibited high K+ induced contraction in isolated rabbit jejunum preparations. Cb.Cr caused a right ward shift in the Ca++ concentration response curve, similar to verapamil. Among various fractions of C bonariensis, only hexane and ethylacetate fractions showed spasmolytic effects. CONCLUSIONS: The crude extract of C. bonariensis contains spasmogenic and spasmolytic constituents, which explains its medicinal use in constipation and diarrhea. [ABSTRACT FROM AUTHOR]

A series of di and triorganotin(IV) complexes of the general formula, R2(Cl)SnL (R= Me: 1; Bu: 2) and R3SnL (R = Bu: 3; Ph: 4) have been synthesized by refluxing equivalent molar ratios of orgnotin(IV) chlorides (R2SnCl2/R3SnCl) with the 1H-1,2,4-Triazole-3-thiol (LH) in dry methanol. The synthesized complexes (1-4) were further treated with CS2 and R2SnCl2/R3SnCl in 1:1:1 molar ratio to yield the homobimetallic complexes of the types R2(Cl)SnLCS2Sn(Cl)R2 (R = Me: 5; Bu: 6) and R3SnLCS2SnR3 (R = Bu: 7; Ph: 8). The ligand and the complexes have been characterized by elemental microanalysis (CHNS), FT-IR and multinuclear NMR (1H&13C), and electron ionization mass spectrometry. IR data demonstrates that the dithiocarbamate donor site of the ligand acts in a bidentate manner and there isa trigonal bipyramidal geometry around Sn(IV) in solid state. 1H and 13C NMR data supports the tetrahedralgeometry with thiol donor sites of the ligand while tetra and penta coordinated environments around dithiocarboxylate bound tin(IV) in solution state. Mass spectrometric data supported well the structures of the synthesized complexes. The homobimetallic derivatives were found more active than mononuclear organotin(IV) compounds and free ligand against various strains of bacteria and fungus.

Objective: To study the attitudes of the patients towards medical students rotating in the dermatology clinic in the King Fahad Hospital of the University (KFHU). Materials and Methods: One hundred and two adult outpatients attending the KFHU in Alkhobar, Saudi Arabia during the period March to June 2004 completed a questionnaire to evaluate their receptiveness towards medical students attending with the dermatologist. Results: Almost 57% preferred physician and medical student participation in their care and 46% welcomed their presence during physical examination. The majority of patients (64.8%) felt comfortable disclosing personal information to the medical student and (68.7%) enjoyed the interaction with the medical students. Patients (63.7%) agreed that the students understood their healthcare needs. Conclusion: The majority of the patients in this study enjoyed their interactions with the students and felt comfortable disclosing information. Some patients want to spend time alone with the physician so permission for medical student participation should be requested.

Tinea capitis is a dermatophyte infection of the scalp the purpose of this study was to define the demographic features, clinical patterns and associated symptoms and signs of tinea capitis in Saudi Arabia. All patients who attended the dermatology clinic of king Fahad Hospital of the University (KFHU) at Al-Khobar, Saudi Arabia and who were diagnosed as tinea capitis between January 1991 and December 2001 were reviewed. The collected data were analyzed using statistical package for social sciences (SPSS). A p value of less than 0.05 was considered as the statistical level of significance. The patients with tinea capitis composed 0.14% of the study population and male to female ratio was 1.8:1. The mean age at presentation was 6.4 + 5.2 years. The most frequent sign was alopecia and the predominant morphological type was the non inflammatory tinea capitis. Micorporum canis was the predominant dermatophyte followed by Trichophyton violaceum.