Serum Levels of Proinflammatory Biomarkers in Military Recruits with and without Metabolic Syndrome.

Objectives: Inflammatory mediators are associated with many chronic diseases; however, their role in metabolic syndrome (Met-S) is not well documented. We therefore aimed to compare the serum markers of inflammation including C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and TNF-ß in young military recruits with and without Met-S. We hypothesized that any significant change in inflammatory markers between the two groups would indicate the role of inflammation in Met-S that would help in future directions for screening and treatment of Met-S. Design and Methods. A total of 2010 adult men, aged 18-30 years, were divided into two groups: with Met-S (N = 488) and without Met-S (N = 1522), according to the International Diabetes Federation definition. We compared the serum levels of inflammatory biomarkers between the two groups. We also studied the correlations between the inflammatory markers and the components of Met-S to explore the biomarker potential of inflammatory markers for screening of Met-S. Logistic regression analysis was performed to test the association between inflammatory markers and Met-S. Results: A large number of subjects in the Met-S group were suffering from obesity. Out of the 2010 total subjects, only 731 (36.4%) had normal fasting blood sugar (FBS), while the prevalence of prediabetes and diabetes was significantly higher in subjects with Met-S. We observed significant increases in serum levels of CRP, MPO, IL-6, and TNF-ß but not TNF-α in subjects with Met-S as compared to subjects without Met-S. All the markers of inflammation showed significant correlations with Met-S, triglycerides (TG), blood pressure, body mass index (BMI), and age; however, none of these markers were correlated with HDL. Logistic regression analysis showed a significant association between Met-S and inflammatory markers. Conclusions: Serum levels of CRP, MPO, IL-6, and TNF-ß are significantly increased in young adults with Met-S. This is probably the first study reporting TNF-ß levels in Met-S. Since a proinflammatory cascade precedes many years before the onset of cardiovascular disease, these inflammatory biomarkers could help in the monitoring of high-risk individuals with Met-S who will be requiring therapeutic intervention.

Laparoscopic sleeve gastrectomy for obesity treatment in adolescents and young adults: a systematic review and meta-analysis.

BACKGROUND: The incidence of obesity has been increasing in younger population, posing a significant impact on adolescents' life and health care system worldwide. METHODS: We critically analyzed the existing literature on the use of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity. We performed an in-depth evaluation of 37 studies and analyzed the effect of LSG in 2300 patients, aged ≤ 22 years. RESULTS: Mean body mass index (BMI) loss after LSG was 17.81 kg/m2. Gastroesophageal reflux was the most common complication. Most of the patients showed remission of comorbidities including hypertension, diabetes, and obstructive sleep apnea after LSG. CONCLUSIONS: These findings suggest that surgical intervention is highly beneficial for reducing BMI in appropriately selected adolescents and young adults suffering from obesity and comorbidities such as life-threatening obstructive sleep apnea.

Inducible Nitric Oxide Synthase iNOS-954-G>C and Ex16+14-C>T Gene Polymorphisms and Susceptibility to Vitiligo in the Saudi Population.

Objective: Vitiligo is an acquired pigmentary skin disorder with regional disappearance of melanocytes. Multigenic inheritance has been proposed in the pathogenesis of vitiligo. The present study aimed to investigate the possible association of inducible nitric oxide synthase polymorphisms iNOS-954-G/C (rs1800482 G>C) and iNOS-Ex16+14-C/T (rs2297518 C>T) with vitiligo in the Saudi population, if any. Methods: We included 120 vitiligo cases and an equal number of age matched healthy controls. Polymerase chain reaction with restriction fragment length polymorphism method was used for the analysis of genetic polymorphisms. Results: The heterozygous (GC), (GC + CC) combined genotype and variant allele; C allele of rs1800482 G>C were associated significantly (p < 0.005, after Bonferroni correction) with increased risk of vitiligo (OR = 3.46, 95% CI = 1.99-6.01, p = 0.001), (OR = 3.30, 95% CI= 1.93-5.65, p = 0.001) and (OR = 1.94, 95% CI = 1.31-2.87, p = 0.001) respectively. When GC genotype of rs1800482 G>C was co-inherited with common genotype (CC) and heterozygous genotype (CT) of rs2297518 C>T, the risk of vitiligo was significantly increased ((OR = 4.51, 95% CI = 2.18-9.33, p = 0.001) and (OR = 3.60, 95% CI = 1.61-8.01, p = 0.001)) respectively. None of the rs1800482 G>C and rs2297518 C>T genotypes and alleles have been associated with non-segmental vitiligo in terms of gender, age of onset, and types of vitiligo. Conclusion: The heterozygous (GC), (GC+CC) combined genotype and variants allele; C allele of rs1800482 G>C, may cause overproduction of NO, which has been linked to melanocyte loss by increasing oxidative stress and decreasing melanocyte adhesion to the extracellular matrix components, and thus could be an associative risk factor for vitiligo.

Association between preventable risk factors and metabolic syndrome.

The risk factors associated with metabolic syndrome (Met-S) including hypertension, hyperglycemia, central obesity, and dyslipidemia are preventable, particularly at their early stage. There are limited data available on the association between Met-S and preventable risk factors in young adults. We randomly selected 2,010 Saudis aged 18-30 years, who applied to be recruited in military colleges. All the procedures followed the guidelines of International Diabetes Federation. The results showed that out of 2,010 subjects, 4088 were affected with Met-S. The commonest risk factors were high blood sugar (63.6%), high systolic and diastolic blood pressures (63.3 and 37.3%), and high body mass index (57.5%). The prevalence of prediabetes and diabetes were 55.2 and 8.4%, respectively. Obesity, diabetes, hypertension, and hypertriglyceridemia were significantly associated with Met-S. The frequency of smoking was significantly linked with the development of Met-S. The prevalence of Met-S was found to be significantly higher in individuals with sedentary lifestyle. In conclusion, the results of this study clearly indicate that military recruits, who represent healthy young adults, are also prone to Met-S. The findings of this study will help in designing preventive measures as well as public awareness programs for controlling the high prevalence of Met-S in young adults.

Recent Trends of Metabolic Syndrome and Its Components in Military Recruits from Saudi Arabia.

Metabolic syndrome (Met-S) constitutes the risk factors and abnormalities that markedly increase the probability of developing diabetes and coronary heart disease. An early detection of Met-S, its components and risk factors can be of great help in preventing or controlling its adverse consequences. The aim of the study was to determine the prevalence of cardio-metabolic risk factors in young army recruits from Saudi Arabia. A total of 2010 Saudis aged 18-30 years were randomly selected from groups who had applied to military colleges. In addition to designed questionnaire, anthropometric measurements and blood samples were collected to measure Met-S components according to the International Diabetes Federation (IDF) criteria. Met-S prevalence was 24.3% and it was higher in older subjects than the younger ones. There were significant associations between Met-S and age, education level and marital status. The most common Met-S components were high fasting blood sugar (63.6%) followed by high blood pressure (systolic and diastolic, 63.3% and 37.3% respectively) and high body mass index (57.5%). The prevalence of pre-diabetes and diabetes were found to be 55.2% and 8.4%, respectively. Hypertriglyceridemia was found in 19.3% and low levels of high-density lipoproteins (HDL) in 11.7% of subjects. In conclusion, there is a high prevalence of Met-S in young adults of Saudi Arabia. There is a need for regular monitoring of Met-S in young populations to keep them healthy and fit for nation building. It is also important to design and launch community-based programs for educating people about the importance of physical activity, cessation of smoking and eating healthy diet in prevention of chronic diseases.

Protective effect of lyophilized sapodilla (Manilkara zapota) fruit extract against CCl4-induced liver damage in rats.

The tropical fruit sapodilla (Manilkara zapota syn. Achras zapota) is a rich source of nutrients, minerals and a myriad of bioactive phytochemicals such as flavonoids and catechins. Pharmacologically, sapodilla has been shown to exhibit anti-bacterial, anti-parasitic, anti-fungal, antiglycative, hypocholesterolemic and anti-cancer effects. However, its influence on hepatic tissue and serum lipids remains obscure. To address this, we used an in vivo model of liver damage to elucidate the effect of lyophilized sapodilla extract (LSE) treatment in carbon tetra chloride (CCl4) intoxicated rats. Exposure of CCl4 resulted in elevation of serum biomarkers of liver damage (aspartate transaminase, alanine aminotransferase, γ-glutamyl transferase and alkaline phosphatase), bilirubin and dysregulation of serum lipid profile (cholesterol and triglycerides). These effects were significantly and dose-dependently reversed by LSE treatment (250 and 500 mg/kg). Administration of LSE also reduced the structural damage caused by CCl4 in the liver. Furthermore, determination of oxidative stress parameters (malondialdehyde and non-protein sulfhydryls) revealed that LSE treatment mitigated CCl4-triggered modulation of both molecules. LSE also showed a strong antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ß-carotene-linoleic acid assays. In conclusion, the present study discloses the hepatoprotective and lipid-lowering effects of lyophilized sapodilla extract against CCl4-induced liver damage, an effect, at least in part, mediated by its antioxidant activity.

Association of Functional Polymorphism in Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene with Vitiligo.

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with susceptibility to autoimmune diseases. The functional polymorphism in PTPN22 at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Present study was aimed to determine whether the PTPN22 C1857T polymorphism confers susceptibility to vitiligo in Saudi Arabians. Genomic DNA was extracted and amplified using tetra primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) method. The frequencies of allele T and genotype CT of PTPN22 C1858T polymorphism were significantly higher, whereas those of allele C and genotype CC were lower in patients as compared with controls (P < 0.0001). The genotype TT was absent in both the patients and controls. It is concluded that PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility. However, additional studies are warranted using large number of samples from different ethnicities and geographical areas.

Methylenetetrahydrofolate Reductase C677T Gene Polymorphism as Risk Factor for Psoriasis in Saudis.

Methylenetetrahydrofolate reductase (MTHFR) has been linked with the etiopathogenesis of psoriasis with inconsistent results. Methylenetetrahydrofolate reductase C677T polymorphism was evaluated in 106 Saudi psoriasis vulgaris patients and 280 matched healthy controls using PCR-RFLP (restriction fragment length plymorphism) technique. The cardiovascular risk factors were also compared in cases and controls. Allele T and genotypes CT and TT were found to be increased while allele C and genotype CC significantly decreased in psoriasis patients as compared with controls (P < .001). These results showed that the T-allele and T-containing genotypes (TT, CT) of MTHFR C677T are significantly linked with psoriasis susceptibility while C-allele and CC genotype are protective for it. Body mass index, fasting glucose, total cholesterol, low-density lipoprotein, triglycerides, and C-reactive protein, known markers for cardiovascular diseases, were found to be significantly elevated in the patient group as compared with the controls. It is concluded that the MTHFR C677T polymorphism increases psoriasis risk in Saudi patients.

Inflammatory gene mRNA expression in human peripheral blood and its association with colorectal cancer.

OBJECTIVE: The present study planned to investigate the changes in the mRNA expression of inflammatory genes and their association with colorectal cancer (CRC). Our findings could be useful for noninvasive early screening of CRC patients. PATIENTS AND METHODS: Venous blood of 20 CRC cases and 15 healthy controls was collected. The mRNA expression of COX-2, TNF-α, NF-κB and IL-6 genes was carried out by using real-time polymerase chain reaction. Relative quantification was done to find out the fold change of these genes. RESULTS: The mean age of cases and controls was 55 and 50 years, respectively. The ΔCt of COX-2, TNF-α, NF-κB and IL-6 genes was significantly (p < 0.05) lower in cases as compared to controls. Subsequently, the mRNA expression of these genes was, respectively, 3.56-, 3.4-, 1.71- and 3.86-fold higher in CRC cases as compared to controls. Positive correlation of ΔCt of COX-2 was found with ΔCt of TNF-α (r = 0.461, p = 0.041) and NF-κB (r = 0.536, p = 0.015) in CRC cases. The mRNA expression of COX-2 was significantly lower in T2 stage, while mRNA expression of NF-κB was significantly lower in both T2 and T3 stages of CRC as compared to T4 stage. CONCLUSION: The increased mRNA expression of COX-2 along with the high mRNA expression of TNF-α, NF-κB and IL-6 genes may be associative risk factors for CRC. COX-2 and NF-κB genes were more expressed in advanced stages of CRC indicating their role in tumor progression. Our findings support the possible role of blood biomarker in the screening of CRC patients in the early stages.

The association of metformin use with vitamin B12 deficiency and peripheral neuropathy in Saudi individuals with type 2 diabetes mellitus.

AIMS: To compare the prevalence of vitamin B12 deficiency and peripheral neuropathy between two groups of type 2 diabetes mellitus (T2DM) patients treated with or without metformin, and to determine factors associated with vitamin B12 deficiency therapy and dietary intake of vitamin B12. METHODS: In this retrospective study, we recruited 412 individuals with T2DM: 319 taking metformin, and 93 non-metformin users. Demographics, dietary assessment for vitamin B12 intakes, and medical history were collected. Participants were assessed for peripheral neuropathy. Blood specimens were collected and checked for serum vitamin B12 levels. The differences between the two groups were analyzed using an independent t-test for continuous data, and the Chi-squared or Fisher's exact test was used for categorical data. The relationship of vitamin B12 deficiency with demographics and clinical characteristics was modeled using logistic regression. RESULTS: The prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively. The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11-20.15, P = 0.036). There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05). Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87-163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47-24.47). CONCLUSION: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (> 2,000 mg/day) and for a longer duration (> 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy.

Protective effects of a natural herbal compound quercetin against snake venom-induced hepatic and renal toxicities in rats.

Echis pyramidum is a highly poisonous viper snake. Previous studies have shown acute phase hepatic and renal toxicities of Echis pyramidum venom (EPV) in rats. This study reports the protective effects of a natural herbal compound quercetin (QRC) on EPV-induced hepatic and renal toxicities in rats. A singly injection of EPV (4.76 mg/kg) caused significant increase in serum biomarkers of liver and kidney function. Pre-treatment of QRC (10 mg/kg) significantly reduced the toxic effects of EPV on functional impairment in liver and kidneys of rats. Administration of QRC also reversed EPV-induced increase in lipid peroxidation and decrease in total thiols. The histopathology of liver showed fat accumulation, focal degeneration and cytoplasmic vacuolation of hepatocytes in EPV treated rats. EPV also caused renal tubular dilation and focal atrophy of glomerular tufts in rat kidneys. Administration of QRC prevented EPV-induced structural tissue damage in liver and kidneys of rats. In conclusion, QRC significantly inhibited the acute phase toxic effects of EPV on liver and kidneys of rats by preventing the oxidative stress in these organs. QRC is also known for its anti-inflammatory, anti-edema, anti-hemorrhagic and PLA2-inhibitory properties and therefore may be regarded as a multi-action antidote against snake venom toxicity.

Scorpion Venom Causes Apoptosis by Increasing Reactive Oxygen Species and Cell Cycle Arrest in MDA-MB-231 and HCT-8 Cancer Cell Lines.

OBJECTIVES: The objective of this study was to examine the effect of scorpion venoms on cancer cell progression, apoptosis, and cell cycle arrest. Scorpion venoms are known to possess numerous bioactive compounds that act against cancer progression by inducing apoptosis. In this study, we have taken the venoms from the following 2 species of scorpion- Androctonus crassicauda and Leiurus quinquestriatus-and tested the anticancer properties of the venom against breast and colorectal cancer cell lines. METHODS: Milking of scorpion venom and culturing the breast and colorectal cancer cell lines were done according to the standard procedure. The venom cytotoxicity was assessed by MTT methods, and the cellular and nuclear changes were studied with phase contrast and propidium iodide staining, respectively. The cell cycle arrest and accumulation of reactive oxygen species were analyzed on a Muse cell analyzer. RESULTS: The venoms exerted cytotoxic effects on breast and colorectal cell lines in a dose- and time-dependent manner. Enhanced apoptotic cells, increase in reactive oxygen species, and cell cycle arrest were observed after challenging these cell lines with scorpion venoms. CONCLUSIONS: Scorpion venom induces apoptosis in breast and colorectal cell lines as reflected by the changes in the cell morphology and cell cycle studies. Furthermore, a high percentage of total reactive oxygen species as well as apoptotic cells also contribute to cell death as observed after venom treatments. To the best of authors' knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by these species of scorpion venoms.

Scorpion Venom Causes Upregulation of p53 and Downregulation of Bcl-xL and BID Protein Expression by Modulating Signaling Proteins Erk1/2 and STAT3, and DNA Damage in Breast and Colorectal Cancer Cell Lines.

Scorpion venoms efficiently block the normal neurotransmitter signaling pathway by prejudicing the ion channel operating mechanism in the body system. Besides its negative effect, venoms also possess some beneficial qualities for humans. They have also been shown to exhibit anticancer properties in various cancer types. This unique property of the venom as an anticancer agent is mainly a result of its role in initiating apoptosis and inhibiting several signaling cascade mechanisms that promote cancer cell proliferation and growth. In this study, we examine the effect of venom on phenotypic changes as well as changes at the molecular levels in colorectal and breast cancer cell lines. A dramatic decrease in cell invasion was observed in both cancer cell lines on venom treatment. Additionally, there was decrease in IL-6, RhoC, Erk1/2, and STAT3 in venom-treated cell lines, providing strong evidence of its anticancer properties. Furthermore, decrease in the expression of antiapoptotic proteins and also upregulation of proapoptotic ones by these lines were observed on venom treatment. Moreover, a vivid picture of DNA damage was also detected on venom treatment. In conclusion, scorpion venom possesses significant potential as an anticancer agent against colorectal and breast cancer cell lines.

Saudi medicinal plants for the treatment of scorpion sting envenomation.

Scorpion sting envenoming poses major public health problems. The treatment modalities include antivenoms, chemical antidotes and phytotherapy, with varying degrees of effectiveness and side effects. In this investigation, we reviewed the use of Saudi medicinal plants for the treatment of scorpion sting patients. The relevant literature was collected using the online search engines including Science Direct, Google and PubMed with the help of specific keywords. We also used the printed and online resources at our institutional library to gather the relevant information on the use of medicinal plants for the treatment of scorpion sting patients. A descriptive statistics was used for data compilation and presentation. The results of this survey showed the use of at least 92 medicinal plants with beneficial effects for treating victims of stings of different scorpion species. These commonly used herbs spanned to 37 families whilst different parts of these plants were employed therapeutically for alleviation of envenomation symptoms. The application of leaves (41%) was preferred followed by roots (19%), whole plant (14%) and seeds (9%). The use of latex (4%), stem (3%), flowers (3%) and bark (3%) was also reported. In some cases, tannin (2%), rhizome (1%) and shoot (1%) were also used. In conclusion, herbal medicines are effectively used for the treatment of patients with scorpion envenomation. This type of medication is free from side effects as observed with chemical antidotes or antivenom therapy. It is important to identify the active ingredients of herbal drugs for improving their therapeutic potential in traditional medicine.

Evaluation of the in vitro antimicrobial activity of selected Saudi scorpion venoms tested against multidrug-resistant micro-organisms.

OBJECTIVES: Scorpion venoms are a rich source of bioactive peptides with promising clinical value that may lead to the discovery and development of new drugs. The present study was designed to evaluate the in vitro antimicrobial activities of the venoms extracted from three medically important Saudi scorpions (Androctonus crassicauda, Androctonus bicolor and Leiurus quinquestriatus). METHODS: Antimicrobial assays were performed using a microplate growth inhibition assay against 10 multidrug-resistant (MDR) micro-organisms (4 Gram-negative bacteria, 2 Gram-positive bacteria and 4 fungi and yeasts) at concentrations ranging from 0 to 20mg/mL of each venom. Following qualitative analysis, dose-response assays were performed for bacterial and fungal killing curves using the MTT colorimetric assay. RESULTS: Among the three tested scorpion venoms, only L. quinquestriatus venom showed significant broad-spectrum antimicrobial activity in a dose-dependent manner from 5 to 20mg/mL. Leiurus quinquestriatus venom inhibited the growth and survival of MDR Escherichia coli (55.2%), Acinetobacter baumannii (50.6%), Klebsiella pneumoniae (35.1%), Pseudomonas aeruginosa (31.3%), Staphylococcus aureus (36.4%), Enterococcus faecalis (47.6%), Candida albicans (31.2%) and Candida glabrata (39.0%), whereas no significant activity against Fusarium oxysporum and Aspergillus flavus was observed. In contrast, the venoms of A. crassicauda and A. bicolor did not show noticeable antimicrobial activity against any of the tested organisms. CONCLUSIONS: The findings of the current study demonstrate that L. quinquestriatus venom possesses antimicrobial activity and thus can be used as a template for designing and development of novel antimicrobial drugs.

Effect of camel milk against renal toxicity in experimental rats.

Most of the antibiotics are associated with considerable side effects. Gentamicin (GM) is one of the most commonly used antibiotics, but has significant nephrotoxic side effects. Hence, the current study is investigating the beneficial role of camel milk (CM) that ameliorate GM unwanted renal defects and dysfunctions in some experimental animals. Sprague-Dawely rats weighing (200-220g) were divided into groups (four) of six. Group 1 (Control) received normal saline (only). Group 2 was given oral administration of CM at the dose of 5ml/rat/day for fifteen days. Group 3 was injected with GM (80mg/kg b.wt., i.p.) for 10 days. Group 4 was first given oral administration of CM at the dose of 5ml/rat/day alone, for five days, and then followed with the administration GM for next 10 days, accordingly. The results show that administration of GM significantly enhanced the kidney weight and levels of renal toxicity markers like urea and creatinine, in addition to decreased levels of blood glucose. Treatment with CM ameliorated and reversed these drastic changes in levels of creatinine, urea and improved renal weight. Glucose levels were also reversed and increased significantly. Furthermore, GM induced renal histological anomalies like degeneration of glomeruli and tubules were suppressed by CM and showed better progress. The present study confirm that pretreatment with CM attenuates GM unwanted, induced renal dysfunction and cellular damage.

An Updated Phytopharmacological Review on Medicinal Plant of Arab Region: Apium graveolens Linn.

Apium graveolens Linn. (Karafs) is used in traditional medicine for the treatment of the various ailments. There is a need to explore and authenticate the pharmacological profile and medicinal importance of the Karafs. In this paper, the literature and the published work on Apium were collected using online resources "Google scholar", "Web of science", "Scopus" and "PubMed". Each of the pharmacological activity was searched individually using the keywords "Apium/Karafs/Apium graveolens + individual pharmacological activity". We documented the most cited and most recent literatures. The current findings illuminate the importance Karafs in the traditional medicine and their impact in treating various diseases. This review strongly supports the fact that the Apium has emerged as a good source of medicine in treating various diseases. There is also a need to isolate the bioactive phytochemicals present in this plant.

Tumor necrosis factor-α and -ß genetic polymorphisms as a risk factor in Saudi patients with schizophrenia.

BACKGROUND: Schizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia. OBJECTIVE: The aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF)-α (-308G/A) and TNF-ß (+252A/G) polymorphisms with schizophrenia susceptibility. SUBJECTS AND METHODS: TNF-α and TNF-ß genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (-308G/A) and TNF-ß (+252A/G) polymorphisms in patients were compared with those in controls. RESULTS: The frequencies of TNF-α (-308) allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (-308G/A) may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-ß (+252A/G) polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-ß (+252A/G) was significantly higher in male patients than in female patients. The distribution of TNF-α (-308G/A) and TNF-ß (+252A/G) polymorphisms was almost similar in schizophrenia patients with negative or positive symptoms. CONCLUSION: TNF-α (-308G/A) and TNF-ß (+252G/A) polymorphisms may increase the susceptibility to schizophrenia in Saudi patients and could be a potential risk factor for its etiopathogenesis. However, further studies are warranted involving a larger sample size to strengthen our findings.

Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin.

Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals. For this, Wistar rats weighing 250±10 g were divided into four groups, including control, STT (40 mg/kg/day), FLX (20 mg/kg/day), and STT+FLX group, respectively. After the dosing period of 4 weeks, the animals were sacrificed, and the blood and brain samples were collected for the analysis of STT, simvastatin acid (STA), FLX, total cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine, dopamine, and hydroxy indole acetic acid. It was found that the coadministration resulted in a significant increase in the bioavailability of STT in the plasma (41.8%) and brain (68.7%) compared to administration of STT alone (p<0.05). The maximum drug concentration (Cmax) of STT was also found to be increased significantly in the plasma and brain compared to that achieved after monotherapy (p<0.05). However, STT failed to improve the pharmacokinetics of FLX up to a significant level. The results of this study showed that the combined regimen significantly reduced the level of cholesterol and triglyceride and increased the level of HDL when compared to STT monotherapy. Furthermore, the coadministration of STT with FLX led to an elevated level of neurotransmitters in the brain (p<0.05). FLX increased the concentration of STT in the plasma and brain. The coadministration of these drugs also led to an improved lipid profile. However, in the long-term, this interaction may have a vital clinical importance because the increase in STT level may lead to life-threatening side effects associated with statins.

The SPARC-related modular calcium binding protein 2 (SMOC2) gene polymorphism in primary glaucoma: a case-control study.

Primary glaucomas are among the most common eye diseases that may potentially result in bilateral blindness. Both genetics and environmental factors are reported to be involved in the etiology of primary glaucomas. Secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding protein 2 (SMOC2) is a matricellular glycoprotein encoded by the SMOC2 gene and known to regulate the expression of extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), which play an important role in the pathogenesis of primary glaucomas. The frequencies of alleles and genotypes of SMOC2 variants were examined in 406 Saudi subjects, including primary open angle glaucoma (POAG, n=140) and primary angle closure glaucoma (PACG, n=64) patients and 202 matched healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotyping of SMOC2 polymorphism (rs13208776) revealed a significantly higher frequency of the heterozygous genotype GA (P<0.01) and a lower frequency of wild type GG genotype (P=0.05) in glaucoma patients compared to the controls. Upon stratification of the patients on the basis of types of glaucoma, PACG patients had a significantly higher frequency of GA genotype as compared to the controls (P<0.01), whereas there was no significant difference between the POAG patient and control groups in frequencies of SMOC2 alleles and genotypes. Further, there was no significant difference in frequency distribution of alleles and genotypes between male and female patients. This study indicates that the GA genotype of SMOC2 (G>A) polymorphism is significantly associated with PACG and may be a risk factor. However, further large-scale studies in the Saudi population as well as in other ethnic populations are needed to confirm this association.