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.

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.

Gastro protecting influence of Topiramate in ethanol produced gastric ulcers in rats.

BACKGROUND: Topiramate (TPM), an antiepileptic drug, is also effective against alcohol dependency, a crucial factor in forming gastric ulcers. There is an increased possibility of patients with compromised gastric conditions getting exposed to TPM, but its effect on gastric ulcers is unknown. This study investigates the implication of acute TPM in ethanol-produced gastric ulceration in rats. MATERIAL AND METHODS: The effect of TPM studied in male 200-225 g Sprague Dawley rats against ethanol-induced gastric ulcers and for gastric secretion and acidity. The factors assessed include gastric secretion and acidity, gastric ulcer score, biochemical and histological changes, NF-kB, and p53 expression. The analysis of data performed by using the Kruskal Wallis test and Dunnett's multiple comparison tests. RESULTS: TPM pretreatment showed gastroprotective effects. It significantly reduced ethanol-induced increased gastric secretion, acidity, and gastric ulcer index and prevented gastric mucus depletion. The ethanol-induced inflammation and apoptosis were also significantly decreased by reducing the increased gastric myeloperoxidase activity and the expression of NF-kB and p53. TPM pretreatment also reduced the ethanol-induced damage to the gastric histology in rats. CONCLUSION: TPM exerted a gastro-protective effect against ethanol-induced gastric ulcers mediated by reducing the gastric ulcer index, preventing a decrease of the mucus levels, reduction in inflammation, damage to gastric histology, and a decrease in the enhanced expression of NF-kB and TPM. Further detailed investigations are essential to understand the chronic influence of TPM on gastric ulcers.

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.

Apolipoprotein E polymorphism is associated with susceptibility to schizophrenia among Saudis.

INTRODUCTION: Apolipoprotein E (APOE) genotypes influence the phenotype of several neurodegenerative disorders including Alzheimer's and Parkinson disease and may affect schizophrenia pathogenesis. This study was undertaken to determine the association between APOE gene polymorphisms and schizophrenia in the Saudi population. MATERIAL AND METHODS: APOE allele and genotype frequencies were studied in 380 Saudi subjects including schizophrenia patients and matched controls using polymerase chain reaction (PCR) and reverse-hybridization techniques. RESULTS: The frequencies of the APOE allele ε2 and genotypes ε2/ε3 and ε2/ε4 were significantly higher in the schizophrenia patients as compared to controls, suggesting that the ε2 allele and its heterozygous genotypes may increase the susceptibility to schizophrenia. In contrast, the frequencies of the ε3 allele and ε3/ε3 genotype were lower in patients as compared to controls, suggesting a protective effect of APOE ε3 for schizophrenia. This study indicated that APOE ε4 was differentially associated with schizophrenia depending on the symptoms as the frequency of the ε4 allele was significantly higher in schizophrenia patients with positive symptoms. By contrast, no significant association between APOE ε4 and schizophrenia patients with negative symptoms was observed. Genotypes ε2/ε2 and ε4/ε4 were absent in patients and controls. Moreover, the age of onset was significantly lower in patients with the APOE ε2/ε3 genotype. There was no significant difference in the frequencies of APOE alleles and genotypes between male and female schizophrenia patients. CONCLUSIONS: The results of this study clearly show that APOE alleles and genotypes are associated with risk of developing schizophrenia and early age of onset in Saudis.

Genetic Variants of Interleukin-10 Gene Promoter are Associated with Schizophrenia in Saudi Patients: A Case-Control Study.

BACKGROUND: Interleukin-10 (IL-10) gene is considered as a potential candidate gene in schizophrenia association studies. The polymorphisms on IL-10 gene have been reported to be linked with susceptibility to the development of schizophrenia within consistent results. AIMS: The aim of this case-control study was to examine whether the -1082A/G, -819T/C, and -592A/C polymorphisms in IL-10 gene are implicated in schizophrenia development in the Saudi population. MATERIALS AND METHODS: Molecular genotyping of IL-10 gene polymorphisms was performed to analyze the genotypes and alleles distribution of three single-nucleotide polymorphisms (SNPs) in patients (n = 181) and healthy individuals as control group (n = 211). RESULTS: The frequencies of GA genotype at -1082, and CC genotype at positions -592 and -819 were significantly higher in schizophrenia patients compared to healthy subjects suggesting that GA, CC, and CC genotypes are susceptible to schizophrenia. The ACC haplotype known to be associated with intermediate production of IL-10 are more prevalent in our schizophrenia patients. On the other hand, genotypes -1082 GG, -819 CT, and -592 CA of IL-10 were more prevalent in healthy controls suggesting protective effects of GA, CT, and CA genotypes against schizophrenia. There was no significant association of IL-10 polymorphisms with sex or positive or negative symptoms of schizophrenia. CONCLUSION: This study indicates that the IL-10 gene polymorphisms play a significant role in the etiology of schizophrenia in Saudi Arabians patients.

Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats.

The present investigation was undertaken, to study the gastro-protective potential of aripiprazole (ARI) an atypical antipsychotic drug in ethanol induced gastric ulcers in rats. ARI (10, 30, 100 mg/kg) was tested for gastric secretion and antiulcer activity in different groups of male Sprague Dawley rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryls (NP-SH), myeloperoxidase (MPO), and serotonin were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ethanol resulted in gastric mucosal injury and a high index of ulcer. Pretreatment with ARI significantly (P < 0.001), reduced the gastric lesions induced by ethanol and also resulted in a significant decrease in the gastric secretion, and total acidity in pylorus ligated rats. ARI also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P < 0.001). The histological changes and the increased MDA and MPO activity were also significantly (P < 0.001) inhibited by ARI. Ethanol induced depletion in the levels of serotonin in the gastric tissue were also significantly restored by pretreatment with ARI (p < 0.001). ARI showed significant antiulcer and gastroprotective activity against ethanol induced gastric ulcers. The gastroprotective effects of ARI may be due to its anti-secretory, antioxidant and anti-inflammatory action and also due to the restoration of the depleted gastric serotonin levels.

HLA-DRB1 association with schizophrenia in Saudi Arabian patients.

OBJECTIVE: This study is aimed to examine the association between HLA-DRB1 alleles frequency and schizophrenia in Saudi Arabs. METHODS: The DRB1 region of major histocompatibility complex was screened by polymerase chain reaction/sequence specific primers (PCR/SSP) in 180 schizophrenia patients and 200 matched controls. RESULTS: The frequency of DRB1*03 was found to be significantly higher in schizophrenia patients as compared to controls, whereas a significantly lower frequency of DRB1*06 was observed in schizophrenia patients as compared to controls. Molecular sub-typing of the most prevalent allele DRB1*03 (30.56%) revealed the presence of DRB1*030101, *030102 alleles. CONCLUSION: The results of this study suggested a positive association between DRB1*03 (DRB1*030101, DRB1*030102) with schizophrenia and a negative association of DRB1*06 with schizophrenia in Saudi Arabs. However it is not clear whether the DRB1*03 alleles have a direct causal role in the etiology of schizophrenia or if they are in direct linkage disequilibrium with another true susceptibility locus. Since schizophrenia is a complex phenotype, it is expected that many factors might act together to produce the final outcome. Further studies are warranted involving larger population to confirm the observations reported in this study.

Trolox ameliorates 3-nitropropionic acid-induced neurotoxicity in rats.

3-nitropropionic acid (3-NPA) is a naturally occurring neurotoxin produced by legumes of the genus Astragalus and Arthrium fungi. Acute exposure to 3-NPA results in striatal astrocytic death and variety of behavior dysfunction in rats. Oxidative stress has been reported to play an important role in 3-NPA-induced neurotoxicity. Trolox is a potent free radical chain breaking antioxidant which has been shown to restore structure and function of the nervous system following oxidative stress. This rapid and efficient antioxidant property of trolox was attributed to its enhanced water solubility as compared with alpha-tocopherol. This investigation was aimed to study the effect of trolox against 3-NPA-induced neurotoxicity in female Wistar rats. The animals received trolox (0, 40 mg, 80 mg and 160 mg/kg, orally) daily for 7 days. 3-NPA (25mg/kg, i.p.) was administered daily 30 min after trolox for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance. Immediately after behavioral studies, the animal's brains were dissected out for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase immunostaining. Administration of 3-NPA alone caused significant depletion of striatal dopamine and glutathione, whereas, the levels of thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) were significantly increased suggesting an elevated level of oxidative stress. Trolox significantly and dose-dependently protected animals against 3-NPA-induced neurobehavioral, neurochemical and structural abnormalities. These results clearly suggest that protective effect of trolox against 3-NPA-induced neurotoxicity is mediated through its free radical scavenging activity.

Pentoxifylline attenuates iminodipropionitrile-induced behavioral abnormalities in rats.

This investigation was undertaken to study the effect of pentoxifylline (PTX) on iminodipropionitrile (IDPN)-induced behavioral abnormalities [excitation with choreiform and circling movements (ECC) syndrome] in rats. The animals were intraperitoneally injected with IDPN (100 mg/kg) daily for 7 days. PTX was administered daily 30 min before IDPN in the doses of 25, 50, and 100 mg/kg for 9 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of the righting reflex. The onset of ECC syndrome was observed on day 8 in the group treated with IDPN alone; all animals in this group became dyskinetic on day 10. Co-treatment with PTX dose dependently delayed the onset time and significantly reduced the incidence and severity of IDPN-induced ECC syndrome; high dose of PTX completely inhibited the abnormal behavioral signs in IDPN-treated rats. Administration of IDPN caused significant depletions in cerebral glutathione and vitamin E levels. Treatment with PTX dose dependently attenuated IDPN-induced oxidative stress in rats. The beneficial effects of PTX against IDPN toxicity may be attributed to its antioxidant and anti-inflammatory properties.

Exacerbation of harmaline-induced tremor by imipramine.

Imipramine is a well-established tricyclic antidepressant which was first approved for the treatment of depression in the late fifties. Antidepressant effect of imipramine is attributed to inhibition of serotonin (5HT) and noradrenaline (NA) reuptake in brain. These monoamines have been implicated in a variety of neurological disorders including tremor. In the present investigation attempt was made to study the effect of imipramine on harmaline-induced tremor in rats. Male Sprague Dawley rats weighing 115+/-2.5 g were given harmaline (10 mg/kg, i.p.) alone or along with imipramine (30 min before harmaline) in doses of 60 and 90 mg/kg respectively. The latency of onset, intensity and duration of tremor and EMG were recorded. To substantiate the role of 5HT in aetiopathology of tremor the above experiment was repeated in the rats pretreated with P-chlorophenylalanine (PCPA), a potent 5HT depleter. The levels of 5HT and 5-hydroxyindole acetic acid (5HIAA) in the brain stem were measured using high performance liquid chromatography. Imipramine dose-dependently exacerbated the duration, intensity and amplitude of EMG following harmaline-induced tremor. Imipramine treatment further decreased harmaline-induced 5HT turnover in the brain stem. However, this was statistically insignificant. Depletion of 5HT produced a significant reduction in the intensity and duration of harmaline-induced tremor. In conclusion, this study suggests that imipramine exacerbates harmaline-induced tremor. Clinical use of imipramine for the treatment of depression in patients who also suffer from tremors may require a close monitoring.

Citalopram, a selective serotonin reuptake inhibitor augments harmaline-induced tremor in rats.

Citalopram, a serotonin reuptake inhibitor (SSRI) is one of the widely used antidepressants. Apart from its antidepressant activity citalopram is also used for anxiety, panic disorders, obsessive-compulsive disorder and behavioral disturbances of dementia. Tremor is the second most common neurological adverse effect in patients receiving treatment with SSRIs. Use of these agents in depressed patients with essential tremor has not been studied. The present study was undertaken to investigate the effect of chronic citalopram treatment on harmaline-induced tremors in rats. Female Sprague-Dawley rats weighing 70+/-2 g were given citalopram in doses of 0, 10, 20 and 40 mg/kg by gavage for 2 weeks. On the 15th day, the rats were given harmaline (10 mg/kg, i.p.) 30 min after the last dose of citalopram. The latency of onset, intensity and duration of tremor and EMG were recorded. Serotonin (5HT) and 5-hydroxy indole acetic acid (5HIAA) were measured in brain stem. Citalopram dose dependently exacerbated the duration, intensity and amplitude of EMG of harmaline-induced tremor. A significant decrease in 5HT turnover (5HIAA/5HT ratio) in the brain stem was observed suggesting a possible role of serotoninergic impairment in citalopram-induced augmentation of harmaline-induced tremor. Clinical implications of these observations warrant further investigation.