Characteristics of Patients Diagnosed With Guillain-Barré Syndrome at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, From 2000 to 2018.

BACKGROUND: Guillain-Barré syndrome (GBS) is the leading cause of non-polio acute flaccid paralysis worldwide, emphasizing the importance of epidemiological studies on this condition. Therefore, well-designed epidemiological studies in different populations can provide a better understanding of the characteristics of patients with GBS and the nature of the disease. To our knowledge, no previous study has attempted to describe the characteristics of patients with GBS in Kingdom of Saudi Arabia (KSA) based on disease subtypes and clinical features in both adult and pediatric patients. This study aimed to assess the frequencies of GBS subtypes and their relationships with patient characteristics and clinical data in a tertiary hospital in Jeddah, KSA. METHODS: This was a retrospective review of patients diagnosed with GBS between January 2000 and January 2018 at King Abdulaziz University Hospital (KAUH), a tertiary center in Jeddah, KSA. RESULTS: In total, 47 patients with GBS (median age: seven years for pediatric and 36 years for adult patients) were included in the current study. There were six male and three female pediatric patients and 19 male and 19 female adult patients. Among patients with GBS who were classified into a specific electrophysiological subtype (n = 28), 13 (46.2%) had acute inflammatory demyelinating polyneuropathy (AIDP), 11 (39%) had an axonal subtype, and four (14%) had Miller Fisher syndrome (MFS). Patients required prolonged hospitalization of approximately 20 ± 22 days (2.83 ± 3.11 weeks). Patients with MFS were more likely to have higher cytoalbuminologic dissociation than those with other subtypes. CONCLUSION: AIDP was the most frequent type of GBS, followed by the axonal type. Patients required prolonged hospitalization of approximately 20 ± 22 days (2.83 ± 3.11 weeks). Patients with MFS were more likely to have higher cytoalbuminologic dissociation than those with other subtypes. GBS type did not show a relationship with ICU admission or mechanical ventilation use. There was no association between specific therapies and different GBS subtypes and no significant difference in outcomes between different patterns of clinical presentation. Intravenous immunoglobulin (IVIg) and plasma exchange (PE) treatments both had the same efficacy in relation to outcomes for patients with GBS.

Hippocampal mitochondrial Ca++ in experimentally induced Alzheimer's disease, link to calpains and impact of vitamin D3 supplementation.

Vitamin D impact on hippocampal mitochondrial Ca++ and calpains was not previously investigated in Alzheimer's disease (AD). The current work aimed to assess the alteration in hippocampal mitochondrial Ca++, ATP & ADP and hippocampal calpains' level in (AlCl3)-induced AD model, and the effect of 2 regimens of vitamin D supplementation on these alterations. METHODS: Forty male Wistar rats were randomized into 4 groups; control, AD (AlCl3100 mg/kg, p.o. daily for 42 days), AD and vitamin D co-treated group (AlCl3 as in AD group with vitamin D3 400 IU/kg/day, p.o. for 42 days) and AD, followed by vitamin D3 group (AlCl3 was given as in AD group for 42 days, then vitamin D3 for two weeks). AD was assessed by hippocampal levels of Aß42, p-tau and spatial memory assessment in Morris water maze. Hippocampal mitochondrial Ca++, ATP and ADP levels besides to calpain-1 & 2 and cytochrome C were assessed in addition to CA1 histological examination. RESULTS: AD animals showed impaired mitochondrial function as denoted by high Ca++ and decreased ATP and ADP and elevated calpain-1 & 2 and cytochrome C. Hippocampal CA1 region showed increased degenerated neurons and reduced thickness of its pyramidal layer. Vitamin D administration minimized the hippocampal mitochondrial impairement induced by AD and mitigated histological alterations even when supplemented post AD establishment. CONCLUSION: Vitamin D administration to AD rats breaks the deleterious loop in the hippocampus that involves increased Ca++, calpain activation, mitochondrial failure, neuronal degeneration and AD disease progression.

Vitamin D improves hepatic alterations in ACE1 and ACE2 expression in experimentally induced metabolic syndrome.

Metabolic Syndrome (MetS) is a term used to describe a cluster of pathophysiological, biochemical, and metabolic criteria; including high Blood Pressure (BP), high cholesterol, dyslipidaemia, central obesity and Insulin Resistance (IR). The Renin Angiotensin System (RAS) has a regulatory function in BP, hydroelectrolyte balance, and cardiovascular function. RAS is composed of angiotensinogen (AGT), (Ang I), (Ang II), (ACE1), (ACE2), (AT1R), (AT2R), and (Ang 1-7). Vitamin D had been proved to act as a protective factor against MetS. Therefore, the study is pursued to explore vitamin D supplementation roles on hepatic RAS in MetS experimental model. At first, 36 males Albino rats were separated into 4 groups and induced to MetS under controlled circumstances for 3 months. Then, data were collected from blood samples, whereas RNA extracted from liver were analyzed using biochemical and statistical analysis tests. As a result, the major finding was proving that vitamin D can balance the expression of ACE1 and ACE2. Also, confirming that it can improve MetS components by elevating HDL and insulin levels while reducing the levels of BP, cholesterol, LDL, TG, GLU, ALT, AST, and IR. These outcomes may give a new insight into the RAS pathways associated with MetS.

The Possible Effects of Vitamin D3 on AlCl3-Induced Histological and Morphometric Alterations of Adult Male Albino Rat Hippocampus.

Context: Alzheimer's disease (AD) is a challenging neurodegenerative disease, and Vitamin D was proved to have neuroprotective effects. Aim: This study was conducted to evaluate the potential neuroprotective effects of Vitamin D3 supplementation on AlCl3-induced AD rat model in different hippocampal subregions (CA1, CA2, and CA3). It also aimed to compare the protective effects of protective versus therapeutic effects of Vitamin D3 regiments on the number of degenerated neurons and the neuronal layer thickness. Materials and Methods: Twenty-four adult male Albino Wister rats were sorted into GI: control; GII: AlCl3-AD model (100 mg/kg) orally for 42 days; GIII: Rats were co-treated with AlCl3 (as GII) and Vitamin D3 (400 IU/kg/day) orally for 42 days; GIV: Rats were treated with AlCl3 for 42 days then with Vitamin D3 for further 2 weeks. Sagittal sections (5 µ) from paraffin-processed brains previously fixed in 10% neutral-buffered formalin were stained with hematoxylin and eosin to evaluate the thickness and number of degenerated neurons in the hippocampal CA1, CA2, and CA3 subregions. Statistical Analysis: The results of this study were expressed as mean ± standard deviation and analyzed by using IBM SPSS Statistics for Windows, version 23 (IBM SPSS, IBM Corp., Armonk, N.Y., USA). P < 0.05 was considered statistically significant. Results: Vitamin D3 supplementations modulated the degenerative changes observed in the hippocampus of AD rat model. In all hippocampal subregions, the thickness was higher in rats treated with Vitamin D3 after the AD induction than rats treated with Vitamin D3 during AD induction. However, this increase was only significant in CA2. Comparison of the number of degenerated neurons between both groups treated with Vitamin D3 revealed that in CA1, the number of degenerated neurons did not statistically differ between the two groups. However, it was insignificantly lower in CA2 in rats treated with Vitamin D3 after the AD induction, and in CA3, it was insignificantly lower in rats treated with Vitamin D3 during the AD induction. Conclusions: Vitamin D3 was found to be effective in ameliorating histological and morphometric alterations in AlCl3-induced AD in rat model and could be proposed as both preventive and therapeutic supplements in high-risk AD patients.

Elevated hippocampal mGlut2 receptors in rats with metabolic syndrome-induced-memory impairment, possible protection by vitamin D.

BACKGROUND: Metabolic syndrome patients are commonly prone to major health problems as cardiovascular diseases, diabetes mellitus, chronic kidney disease, cancer and neuropsychological complications including dementia. OBJECTIVES: This research investigates mechanisms linking metabolic syndrome to cognitive impairment and possible impact of vitamin D supplementation. METHODS: Forty male Wistar rats were divided into 4 groups. Control, metabolic syndrome (20% fructose solution in drinking water for 12 weeks, vitamin D supplemented (500 IU/kg/day)) and metabolic syndrome supplemented with vitamin D. Animals were assessed for spatial memory, hippocampal expression of SNAP 25, VAMP and mGlut2 receptor and hippocampus histological examination. Animals with metabolic syndrome showed prolonged acquisition and retention latencies in morris water maze, decreased hippocampal expression of SNAP 25 and VAMP and increased mGlut2 expression. Histologically CA1, CA3 regions and dentate nucleus revealed increase in degenerated neurons and glia cells with decreased pyramidal cell layer thickness. Vitamin D supplementation mitigated alterations induced by metabolic syndrome. CONCLUSIONS: Metabolic syndrome decreased hippocampal synaptic proteins and altered glutamatergic transmission and increased hippocampal neuronal degeneration. Vitamin D supplementation offered neuroprotective effects.

Uncoupling proteins: are they involved in vitamin D3 protective effect against high-fat diet-induced cardiac apoptosis in rats?

This study aimed to assess the impact of high-fat diet (HFD) and vitamin D3 supplementation on cardiac apoptosis, inflammation, oxidative stress, and cardiac uncoupling proteins (UCPs) 2&3 expression. Forty rats were fed either (45%) or (10%) fat diet with or without vitamin D3 (500 U/kg/day) for 6 months, then cardiac tissue expression of Bax, Bcl2, Fas, Fas-L (markers for apoptotic pathways), TNF-α, MDA7, GPX1 (inflammatory and oxidative markers) and UCP 2&3 were assessed. Results revealed the enhancement of intrinsic and extrinsic cardiomyocyte apoptosis cascades and increased inflammatory and oxidative burdens on the heart in HFD rats. Downregulation of UCP2 and upregulation of UCP3 gene expression at 6 months. After vitamin D3 supplementation with HFD, cardiac apoptotic, inflammatory and oxidative markers were mitigated and expression of UCP3 was downregulated and UCP2 was upregulated. This work highlights the novel cardioprotective effect of vitamin D3 in the experimental model of HFD feeding through the downregulation of UCP3.

Renin-Angiotensin System Implications to COVID-19 Comorbidities.

The role of the renin-angiotensin system (RAS) and its pharmacological modulators in the susceptibility and outcomes of SARS CoV-2 pandemic (COVID-19) has been much discussed recently. Angiotensin-converting enzyme type 2 (ACE2) has attracted much attention and debate in relevance to COVID-19. It not only acts as the receptor to which the SARS CoV-2 virus binds to be introduced into cells but also balances the effects of angiotensin II offering anti-inflammatory and antifibrotic protective actions to different organs. This mini-review aims to shed some light on the possible involvement of ACE2 and RAS alternate pathways in the comorbidities and clinical findings observed in COVID-19 patients.

Vitamin D3 favorable outcome on recognition memory and prefrontal cortex expression of choline acetyltransferase and acetylcholinesterase in experimental model of chronic high-fat feeding.

Aim of the study: High-fat diet (HFD) consumption and insufficient vitamin D levels are globally increasing phenomena. The present study assessed the effect of chronic HFD feeding with and without vitamin D supplementation on recognition memory and prefrontal cortex expression of choline acetyltransferase (CAT) and acetylcholinesterase (Achase).Materials and methods: Forty male Wistar rats were subjected to four dietary regimens (n = 10); control diet (10% fat), control + vitamin D3, high-fat diet (HFD 45% fat) and HFD + vitamin D3 for 6 months. Rats were tested for the novel object recognition test, and their prefrontal cortices were assessed for expression of CAT and Achase.Results: Recognition memory was impaired in HFD-fed rats compared to control rats as evidenced by significantly decreased discrimination index in the novel object recognition test. Moreover, CAT expression was significantly decreased while Achase expression was significantly increased in the prefrontal cortex of HFD-fed rats. Vitamin D3 supplementation with HFD significantly increased the exploration of the novel object and the discrimination index and attenuated the alterations in the prefrontal cortex CAT and Achase expression.Conclusions: The present findings support the potential effect of vitamin D on recognition memory and cholinergic transmission in the prefrontal cortex and add to the pathophysiology of HFD consumption.

Effect of vitamin D3 on thyroid function and de-iodinase 2 expression in diabetic rats.

OBJECTIVE: This study aimed to assess the effect of vitamin D3 administration to diabetic rats on thyroid profile and deiodinase 2 (D2). METHODS: Thirty male Wistar rats were included into three groups; control, streptozotocin-induced diabetic and diabetic supplemented with vitamin D3 groups. Ten weeks later, serum levels of free T4, free T3 and TSH were measured. Tissue homogenates from liver, kidney, muscle, femur bone, heart and brain were obtained and assessed for D2 mRNA. RESULTS: Diabetic rats demonstrated significant increase in free T4 and significant decrease in free T3. These changes were ameliorated by vitamin D3 administration. D2 mRNA was significantly reduced in all tissue homogenates obtained from diabetic rats, while vitamin D3 treatment significantly enhanced D2 in liver and brain homogenates. CONCLUSION: Diabetes mellitus inhibited peripheral conversion of T4 into T3 secondary to reduction in D2 expression. Vitamin D3 greatly corrected the alterations in thyroid profile and D2 expression.

Vitamin D3 improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats.

Complications of diabetes mellitus include cognitive impairments and functional changes in the brain. The present study aimed to investigate the possible beneficial effect of vitamin D3 on episodic memory and cholinergic transmission in the prefrontal cortex of streptozotocin-induced diabetic rats. Thirty male Wistar rats (150-200 g) were included into control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg in citrate buffer. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in corn oil for 10 weeks. Then rats were subjected to novel object recognition test to examine for episodic memory. Animals were sacrificed under diethyl ether anesthesia and prefrontal cortices were dissected to measure the activity of choline acetyl transferase (CAT) and acetyle choline esterase (ACE) enzymes to assess for cholinergic transmission. Diabetic rats spent significantly less time exploring the novel object compared to control animals. Vitamin D3 significantly attenuated the diabetes-induced impairment so that animals again spent significantly more time exploring the novel object. The CAT activity was significantly decreased in diabetic animals while the ACE activity was significantly increased compared to control non-diabetic animals. Diabetes-induced alterations in enzyme activity in the prefrontal cortex were mitigated by vitamin D3 supplementation. The present findings demonstrate the potential effect of vitamin D3 supplementation on cognitive function in diabetic animals. It is possible that this effect is mediated through enhancing the prefrontal cortex cholinergic transmission.

Grape Seed Proanthocyanidins Attenuate Anxiety-Like Behavior in an Experimental Model of Dietary-Induced Hypercholesterolemia in Rats.

OBJECTIVE: Grape seed proanthocyanidins have many health-protective effects. The present work aimed to assess their possible anxiolytic effects in dietary-induced hypercholesterolemia in rats. METHODS: 30 Male Wistar rats were divided into 3 groups (n = 10): control (normal chow), high cholesterol (cholesterol and cholic acid chow) and high cholesterol + grape seed extract (hypercholesterolemic chow + grape seed extract, 100 mg/kg body weight/day). After 4 months, total cholesterol levels and animals' behavior in the open field and elevated plus maze were assessed. RESULTS: High-cholesterol diet elevated cholesterol levels (p < 0.001 vs control group), however, grape seed administration ameliorated this elevation (p < 0.001 vs high-cholesterol untreated group). In the open field, hypercholesterolemic rats showed increased periods of immobility (138 ± 20.3 seconds (s) vs 96.9 ± 14.5 in control rats p < 0.001) and time latency to enter field center (109 ± 18.3 s compared to 40.8 ± 10.5 s in the control group p < 0.001). Both parameters were reduced by grape seed treatment (p < 0.01, p < 0.001 vs the untreated hypercholesterolemic group, respectively). Elevated plus maze testing demonstrated higher closed-arm entries (5.5 ± 1.1 in hypercholesterolemic animals vs 3 ± 1.1 in the control group p < 0.001) and lower percentage of time spent in open arms (19.7 ± 3.5 % vs 35.8 ± 4.8 % in control rats p < 0.001). Grape seed extract significantly enhanced the percentage of time spent in open arms (p < 0.001 compared to hypercholesterolemic rats). CONCLUSION: The present results highlight the possible anxiolytic effect of grape seed proanthocyanidins in dietary-induced hypercholesterolemia.

Estrogen deficiency reduces the expression of estrogen receptor-beta in Wistar rats` periodontal tissues.

OBJECTIVE: To assess the effect of ovariectomy on the expression of estrogen receptor-beta (ER-beta) in periodontal ligament and alveolar bone. METHODS: This animal study was conducted at King Fahad Research Center, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia from March to October 2012. Thirty 12-week-old female Wistar rats were divided into 2 groups (15 each): ovariectomized (OVX) and sham-operated. Levels of estrogen and progesterone in the sera were measured using the enzyme linked immunosorbent assay (ELISA). To detect the expression of ER-beta, immunostaining was performed on the tibia, alveolar bone, and periodontal ligament specimens followed by quantitative histomorphometric analysis. RESULTS: Estrogen (p=0.001) and progesterone (p=0.007) levels were significantly decreased in the OVX rats compared to their controls. Histologically, the thickness and area percentage of the tibia and alveolar bone trabeculae were significantly reduced in OVX rats compared to the controls (p=0.001). The periodontal ligament fibers in the control group exhibited well-organized and appropriately oriented fibers, while in the OVX group they appeared disrupted with loss of orientation. The ER-beta expression in the OVX rats was significantly decreased in the periodontal tissues (p=0.005) and tibia (p=0.008). CONCLUSION: Estrogen deficiency resulted in a significant decrease in the expression of ER-beta in both tibia and periodontal tissues.

An evidence for the transcriptional regulation of iodothyronine deiodinase 2 by progesterone in ovarectomized rats.

Recent literature lacks studies on the effects of progesterone withdrawal on peripheral conversion of thyroxin (T4) into triiodothyronine (T3) by iodothyronine deiodinase 2 (D2) in different body tissues. The present study aimed to assess the possible relation of progesterone to T4, T3, and D2 in ovarectomized rats. Thirty female Wistar rats were included into a sham-operated control group and an ovarectomized group. Four months following the surgical procedures, measurements of estradiol, progesterone, free T4, free T3, and thyroid-stimulating hormone (TSH) were done. Also, estradiol/progesterone and T4/T3 ratios were calculated. Tissue homogenates from the kidney, liver, brain, thyroid, mandible, and femur were used to assess expression of D2 mRNA. The estradiol/progesterone ratio showed a significant increase in ovarectomized rats. T4 showed a significant increase in contrast to T3 which showed a highly significant decrease following ovariectomy. The T4/T3 ratio was significantly increased in ovarectomized rats. In addition, D2 expression was significantly attenuated in all tissue homogenates of the ovarectomized group. The present work showed a significant positive correlation between T4 and T3 in the sham-operated control rats, which was abolished in ovarectomized rats. A negative significant correlation between progesterone and T4 was revealed in ovarectomized rats. There was also a significant positive correlation between progesterone and D2 expression in the ovarectomized group. The results of the present study hypothesize that progesterone withdrawal may underlie the decrement in D2 expression, with consequent reduction in the peripheral conversion of T4 into T3 leading to a hypothyroid state.

Brief assessment of supine heart rate variability in normal weight, overweight, and obese females.

BACKGROUND: Little research has been conducted on the heart rate variability (HRV) parameters in late adolescent females. The present study aimed to assess HRV time and frequency domain parameters in overweight and obese late adolescent females. Also to assess any possible correlation between HRV parameters and obesity indices in that particular age group. SUBJECTS AND METHODS: Fifteen-minute period of standardized ECG recording was implemented to record HRV time and frequency parameters in 42 normotensive euglycemic female medical students aged (18-21 years); lean (n = 13), overweight (n = 13), and obese (n = 16). For the analysis of results, 2.5-minute data were used. RESULTS: Root mean squares of successive differences between adjacent RR intervals (rMSSD) and high-frequency (HF) power were significantly decreased in overweight and obese late adolescent females. Parameters reflecting sympathetic activity which include low-frequency (LF) power and LF/HF ratio showed significant increase in overweight group. Interestingly, LF power was significantly reduced in obese group while the LF/HF ratio was insignificantly different. No significant correlations were observed between HRV indices and parameters of total or visceral obesity in the study groups. CONCLUSION: HRV indices showed sympathetic hyperactivity in overweight late adolescent females and diminished sympathetic response in matching obese group. Both overweight and obese females showed decreased protective vagal influence on the heart.

Estrogenicity of outer scales of onion on uteri of immature mice.

We aimed to investigate the estrogen-like activities of the outer scales of onion and garlic on the uteri of immature mice. This work compared the estrogenic effects induced by estradiol with the effects of plant extract (onion, garlic) in models of immature mice (n = 72). The animals were divided into 6 groups, with 12 animals in each group, as follows: Group I (control group), Group II (estradiol-treated group), Group III (onion extract treated group), Group IV (onion extract treated group after blockage of estrogen receptors), Group V (garlic extract treated group), and Group VI (garlic extract treated group after blockage of estrogen receptors). Uterine wet weight/body mass ratios were determined. Uterotrophic bioassay, immunohistochemical assay for estrogen receptor and proliferative marker Ki67, uterine contractility, and serum estrogen levels were investigated. Onion extract induced proliferative changes in the uterus, it also increased the uterine mass and epithelial cell height. Also, the frequency and amplitude of myometrial contractility were significantly increased in the group treated with onion extract. This estrogenic activity could be attributed to the quercetin and daidzein content, and activation of estrogenic receptors, as these effects disappeared after blockage of E2 receptors. Our results support the possible estrogenic properties of the onion extract, which could be attributed to quercetin and daidzein, but not that of garlic extract.