Optimized mucoadhesive niosomal carriers for intranasal delivery of carvedilol: A quality by design approach.

Carvedilol (CV), a ß-blocker essential for treating cardiovascular diseases, faces bioavailability challenges due to poor water solubility and first-pass metabolism. This study developed and optimized chitosan (CS)-coated niosomes loaded with CV (CS/CV-NS) for intranasal (IN) delivery, aiming to enhance systemic bioavailability. Utilizing a Quality-by-Design (QbD) approach, the study investigated the effects of formulation variables, such as surfactant type, surfactant-to-cholesterol (CHOL) ratio, and CS concentration, on CS/CV-NS properties. The focus was to optimize specific characteristics including particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and mucin binding efficiency (MBE%). The optimal formulation (Opt CS/CV-NS), achieved with a surfactant: CHOL ratio of 0.918 and a CS concentration of 0.062 g/100 mL, using Span 60 as the surfactant, exhibited a PS of 305 nm, PDI of 0.36, ZP of + 33 mV, EE% of 63 %, and MBE% of 57 %. Opt CS/CV-NS was characterized for its morphological and physicochemical properties, evaluated for stability under different storage conditions, and assessed for in vitro drug release profile. Opt CS/CV-NS demonstrated a 1.7-fold and 4.8-fold increase in in vitro CV release after 24 h, compared to uncoated CV-loaded niosomes (Opt CV-NS) and free CV, respectively. In vivo pharmacokinetic (PK) study, using a rat model, demonstrated that Opt CS/CV-NS achieved faster Tmax and higher Cmax compared to free CV suspension indicating enhanced absorption rate. Additionally, Opt CV-NS showed a 1.68-fold higher bioavailability compared to the control. These results underscore the potential of niosomal formulations in enhancing IN delivery of CV, offering an effective strategy for improving drug bioavailability and therapeutic efficacy.

Topical Administration of Verapamil in Poly(ethylene glycol)-Modified Liposomes for Enhanced Sinonasal Tissue Residence in Chronic Rhinosinusitis: Ex Vivo and In Vivo Evaluations.

Verapamil is a calcium channel blocker that holds promise for the therapy of chronic rhinosinusitis (CRS) with and without nasal polyps. The verapamil-induced side effects limit its tolerated dose via the oral route, underscoring the usefulness of localized intranasal administration. However, the challenge to intranasal administration is mucociliary clearance, which diminishes localized dose availability. To overcome this challenge, verapamil was loaded into a mucoadhesive cationic poly(ethylene glycol)-modified (PEGylated) liposomal carrier. Organotypic nasal explants were exposed to verapamil liposomes under flow conditions to mimic mucociliary clearance. The liposomes resulted in significantly higher tissue residence compared with the free verapamil control. These findings were further confirmed in vivo in C57BL/6 mice following intranasal administration. Liposomes significantly increased the accumulation of verapamil in nasal tissues compared with the control group. The developed tissue-retentive verapamil liposomal formulation is considered a promising intranasal delivery system for CRS therapy.

Cold exposure impairs extracellular vesicle swarm-mediated nasal antiviral immunity.

BACKGROUND: The human upper respiratory tract is the first site of contact for inhaled respiratory viruses and elaborates an array of innate immune responses. Seasonal variation in respiratory viral infections and the importance of ambient temperature in modulating immune responses to infections have been well recognized; however, the underlying biological mechanisms remain understudied. OBJECTIVE: We investigated the role of nasal epithelium-derived extracellular vesicles (EVs) in innate Toll-like receptor 3 (TLR3)-dependent antiviral immunity. METHODS: We evaluated the secretion and composition of nasal epithelial EVs after TLR3 stimulation in human autologous cells and fresh human nasal mucosal surgical specimens. We also explored the antiviral activity and mechanisms of TLR3-stimulated EVs against respiratory viruses as well as the effect of cool ambient temperature on TLR3-dependent antiviral immunity. RESULTS: We found that polyinosinic:polycytidylic acid, aka poly(I:C), exposure induced a swarm-like increase in the secretion of nasal epithelial EVs via the TLR3 signaling. EVs participated in TLR3-dependent antiviral immunity, protecting the host from viral infections through both EV-mediated functional delivery of miR-17 and direct virion neutralization after binding to virus ligands via surface receptors, including LDLR and ICAM-1. These potent antiviral immune defense functions mediated by TLR3-stimulated EVs were impaired by cold exposure via a decrease in total EV secretion as well as diminished microRNA packaging and antiviral binding affinity of individual EV. CONCLUSION: TLR3-dependent nasal epithelial EVs exhibit multiple innate antiviral mechanisms to suppress respiratory viral infections. Furthermore, our study provides a direct quantitative mechanistic explanation for seasonal variation in upper respiratory tract infection prevalence.

Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis.

Systemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.

Critical quality attributes in the development of therapeutic nanomedicines toward clinical translation.

Nanomedicine is a rapidly emerging field with several breakthroughs in the therapeutic drug delivery application. The unique properties of the nanoscale delivery systems offer huge advantages to their payload such as solubilization, increased bioavailability, and improved pharmacokinetics with an overall goal of enhanced therapeutic index. Nanomedicine has the potential for integrating and enabling new therapeutic modalities. Several nanoparticle-based drug delivery systems have been granted approval for clinical use based on their outstanding clinical outcomes. Nanomedicine faces several challenges that hinder the realization of its full potential. In this review, we discuss the critical formulation- and biological-related quality features that significantly influence the performance of nanoparticulate systems in vivo. We also discuss the quality-by-design approach in the pharmaceutical manufacturing and its implementation in the nanomedicine. A deep understanding of these nanomedicine quality checkpoints and a systematic design that takes them into consideration will hopefully expedite the clinical translation process. Graphical abstract.

Delivery of neurotrophic factors in the treatment of age-related chronic neurodegenerative diseases.

Introduction: Neurodegenerative diseases are those wherein the neurons in the brain or peripheral nervous system lose their function, eventually culminating in neuronal death. Aging acts as the predominant factor here due to the reduced protein turnover rate in aging cells. As neurotrophic factors possess imperative roles in protecting the neurons and restoring their functionality, design of different modalities to deliver them to the brain would significantly enhance the therapeutic benefits.Areas covered: This review covers the various mechanisms of neurodegeneration, its molecular link with aging, different neurotrophic factor classes and their potentials, current treatment strategies, the challenges associated with the delivery of neurotrophic factors, administration routes, design of different delivery vehicle design, alternative modalities of delivery, and the clinical translational challenges of these strategies.Expert opinion: A deeper molecular level understanding about the complexity of neurodegeneration, discovery of potential biomarkers, which helps identifying the right targets, finding the accurate animal model completely recapitulating the human scenario, and a validated design of clinical trials would immensely help in overcoming the present challenges. The substantial developments in the field of gene therapy, usage of small molecules and peptide mimetics, combinatory approaches, etc. definitely give brighter hopes.

Sustained Delivery of Carfilzomib by Tannic Acid-Based Nanocapsules Helps Develop Antitumor Immunity.

A group of chemotherapeutic drugs has gained increasing interest in cancer immunotherapy due to the potential to induce immunogenic cell death (ICD). A critical challenge in using the ICD inducers in cancer immunotherapy is the immunotoxicity accompanying their antiproliferative effects. To alleviate this, a nanocapsule formulation of carfilzomib (CFZ), an ICD-inducing proteasome inhibitor, was developed using interfacial supramolecular assembly of tannic acid (TA) and iron, supplemented with albumin coating. The albumin-coated CFZ nanocapsules (CFZ-pTA-alb) attenuated CFZ release, reducing toxicity to immune cells. Moreover, due to the adhesive nature of the TA assembly, CFZ-pTA-alb served as a reservoir of damage-associated molecular patterns released from dying tumor cells to activate dendritic cells. Upon intratumoral administration, CFZ-pTA-alb prolonged tumor retention of CFZ and showed consistently greater antitumor effects than cyclodextrin-solubilized CFZ (CFZ-CD) in B16F10 and CT26 tumor models. Unlike CFZ-CD, the locally injected CFZ-pTA-alb protected or enhanced CD8+ T cell population in tumors, helped develop splenocytes with tumor-specific interferon-γ response, and delayed tumor development on the contralateral side in immunocompetent mice (but not in athymic nude mice), supporting that CFZ-pTA-alb contributed to activating antitumor immunity. This study demonstrates that sustained delivery of ICD inducers by TA-based nanocapsules is an effective way of translating local ICD induction to systemic antitumor immunity.

Lycopene solid lipid microparticles with enhanced effect on gingival crevicular fluid protein carbonyl as a biomarker of oxidative stress in patients with chronic periodontitis.

Lycopene (LP), a naturally occurring carotenoid in red-coloured fruits, especially tomatoes, has a pivotal role in counteracting the deleterious effect of oxidative stress on periodontal tissues. The aim of this study is to prepare solid lipid microparticles (SLMs) encapsulating LP and to assess their biochemical and clinical effects in the management of chronic periodontitis. Optimization of SLMs was performed by assessing particle size and LP entrapment efficiency. Clinical study included 16 chronic periodontitis patients allocated into two groups, Group I was managed by scaling and root planing (SRP) and local delivery of LP loaded SLMs, while Group II was managed by SRP only. Protein carbonyl (PC) levels as a biomarker of oxidative stress and drug concentration in gingival crevicular fluid (GCF) were assessed at different time intervals. Results revealed that optimum formula of SLMs had a particle size of 77.28 µm and entrapped 98.03% of LP. SLMs recorded 30 d of drug release with no burst effect. Patients treated with LP SLMs showed significantly lower levels of PC after SRP compared to those treated with SRP only, in addition to improvement in the measured clinical parameters. In conclusion, locally delivered LP SLMs along with SRP could have a protective effect over periodontal tissues and it has the ability to decrease oxidative damage of proteins in diseased periodontium.

Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals.

Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of ovarian cancer, but the full potential is yet to be realized. To facilitate IP chemotherapy of ovarian cancer, we developed an in-situ crosslinkable hydrogel depot containing paclitaxel (PTX) nanocrystals (PNC). PNC suppressed SKOV3 cell proliferation more efficiently than microparticulate PTX precipitates (PPT), and the gel containing PNC (PNC-gel) showed a lower maximum tolerated dose than PPT-containing gel (PPT-gel) in mice, indicating greater dissolution and cellular uptake of PNC than PPT. A single IP administration of PNC-gel extended the survival of tumor-bearing mice significantly better than Taxol, but PPT-gel did not. These results support the advantage of PNC over PPT and demonstrate the promise of a gel depot as an IP drug delivery system.

Hot-melts in buccoadhesive patches: an approach for bioavailability enhancement of highly-metabolized drugs with short elimination half-life.

The present study deals with the inclusion or incorporation of hot-melts into buccoadhesive patches. Our aim is to develop a patient-friendly dosage form that is capable of extending release of short elimination half-life drugs so to decrease dosing frequency and to increase the bioavailability of highly-metabolized drugs with the ultimate aim of dose reduction. Tizanidine hydrochloride (TIZ) was used as a model drug.TIZ was incorporated into Compritol-based hot-melts, and then further formulated into buccal patches prepared using HPMC, PVA and Polyox. A Central Composite Face-centered Design was employed to statistically optimize the formulation variables; HPMC solution/PVA solution weight ratio, Compritol/TIZ ratio in the hot-melts and percentage Polyox. The optimized formula suggested by the software was successful in controlling drug release, where 85% of TIZ was released after 4 h and the patch showed acceptable mucoadhesion properties. Pharmacokinetic parameters of TIZ from the optimized formula were compared to those of the immediate release tablet, Sirdalud®, as reference in human volunteers using a randomized crossover design. Significant increase was observed for Cmax, Tmax, AUC(0-12) and AUC(0-1). The increase in relative bioavailability of TIZ from the optimized formula was 2.57 folds.

Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl: in vitro and in vivo performance.

Tizanidine HCl is a skeletal muscle relaxant that suffers from extensive hepatic metabolism resulting in 34-40% oral bioavailability. It also suffers from short half-life (2.1-4.2h) that necessitates frequent administration thus reducing patient compliance. In addition, tizanidine HCl is water soluble, so it is a challenging candidate for controlled drug delivery. In our study, tizanidine was encapsulated in chitosan lactate beads cross-linked with sodium tripolyphosphate. The beads were further incorporated into chitosan lactate wafer to be easily applied to buccal mucosa, aiming to bypass the hepatic metabolism. A central composite face-centered design was applied to statistically optimize the formulation variables; tripolyphosphate concentration, chitosan lactate concentration and polymer/drug ratio. The optimized formula suggested by the software composed of; 3.03% tripolyphosphate, 4.92% chitosan lactate and 2.13 polymer/drug ratio. It provided encapsulation efficiency of 56.5% and controlled tizanidine release over 8h. It is also characterized by being mucoadhesive and nonirritant. Pharmacokinetic parameters of tizanidine from the optimized formula were compared to those of the immediate release tablet, Sirdalud(®), as reference in human volunteers using a randomized crossover design. Significant increase was observed for Tmax and AUC(0-∞). The increase in relative bioavailability of TIZ from the optimized formula was 2.27 fold.

Flow acceleration time and ratio of acceleration time to ejection time for prosthetic aortic valve function.

OBJECTIVES: We sought to evaluate whether ejection dynamics, particularly acceleration time (AT) and the ratio of AT to ejection time (ET), can differentiate prosthetic aortic valve (PAV) stenosis from controls and prosthesis-patient mismatch (PPM). BACKGROUND: Diagnosing PAV stenosis, especially in mechanical valves, may be challenging and has significant clinical implications. METHODS: Doppler echocardiography was quantitated in 88 patients with PAV (44 mechanical and 44 bioprosthetic; age 63 ± 16 years; valve size range 18 to 25 mm) of whom 22 patients had documented PAV stenosis, 22 had PPM, and 44 served as controls. Quantitative Doppler parameters included ejection dynamics (AT, ET, and AT/ET) and conventional PAV parameters. RESULTS: Patients with PAV stenosis had significantly lower effective orifice area (EOA) values and higher gradients compared with controls and PPM. Flow ejection parameters (AT and AT/ET) were significantly longer in the stenotic valves compared with PPM and controls (respective values for AT: 120 ± 24 ms, 89 ± 16 ms, and 71 ± 15 ms; for AT/ET: 0.4, 0.32, and 0.3, p ≤ 0.001). Patients with PPM had gradients and ejection dynamics that were intermediate between normal and stenotic valves. Receiver-operator characteristic (ROC) curve analysis showed that AT and AT/ET discriminated PAV stenosis from PPM and controls (area under ROC curve = 0.92 and 0.88, respectively). Combining AT with the conventional Doppler velocity index gave the highest area under the curve of 0.98 but was not statistically different from that of AT alone (p = 0.12). A cutoff of AT = 100 ms had a sensitivity and specificity of 86% for identifying PAV stenosis; for an AT/ET = 0.37, the sensitivity and specificity were 96% and 82%, respectively. Analysis by valve type (mechanical and biological) revealed similar results; however, biological valves had slightly higher areas under the curve for all systolic time intervals. CONCLUSIONS: Ejection dynamics through PAV, particularly AT and AT/ET, are reliable angle-independent parameters that can help evaluate valve function and identify PAV stenosis.

Smoking in Saudi Arabia and its relation to coronary artery disease.

OBJECTIVES: The health hazards related to smoking are well known. Smoking is a recognized risk factor for coronary artery disease (CAD). Despite rejection of smoking by the Saudi community, we are still seeing smokers in our population. This study is designed to determine the prevalence of smoking in the Kingdom of Saudi Arabia (KSA), and to find out its relation to CAD. This study is part of the Coronary Artery Disease In Saudis (CADIS) study. METHODS: This health survey was conducted by collecting data regarding smoking status among adult Saudis aged between 30 and 70 years of both sexes in KSA over a five year period from 1995 up to 2000. The study sample was of normal distribution and representative of all regions of KSA. The data were analyzed to provide the prevalence of smoking and its relation with CAD. RESULTS: The total number of subjects was 17,350, and current smokers were 2217; accordingly the overall prevalence of smoking among Saudis was 12.8%. Males (1555) were significantly smoking more than females (662) with a prevalence of 18.7% and 7.3%, respectively (P < 0.0001). Smoking is more prevalent among Saudis living in urban, northern, western, and eastern regions compared to other regions of KSA. Smokers are more likely to develop CAD compared to non-smokers (P < 0.0001). CONCLUSIONS: Smoking is a prevalent health problem among Saudis that requires intervention for eradication. We found clear association between cigarettes smoking and CAD particularly among males. Persistent education of the health hazards related to smoking is recommended particularly at early age in-order to prevent initiation of smoking.

Hyperlipidemia in Saudi Arabia.

OBJECTIVE: To determine the prevalence of hyperlipidemia among Saudis of both genders in rural and urban communities. METHODS: Selected Saudis in the age group of 30-70 years were studied over a 5-year period between 1995 and 2000 in Saudi Arabia. Data were obtained from history, physical examination, and analysis of fasting plasma lipids. The data were analyzed to classify individuals with hypercholesterolemia (HC) (total cholesterol > or =5.2 mmol/l), and hypertriglyceridemia (HT) (total triglycerides > or =1.69 mmol/l). Logistic regression analysis was performed to provide a risk assessment model and correlation with other coronary artery disease (CAD) risk factors. RESULTS: The number of study samples included in the final analysis was 16,819. The prevalence of HC was 54% with mean cholesterol level of 5.4+/-1.52 mmol/l. Prevalence of HC among males was 54.9% and 53.2% for females, while 53.4% among urban Saudis and 55.3% for rural Saudis. Hypertriglycemia prevalence was 40.3% with mean triglycerides level of 1.8+/-1.29 mmol/l. Males had statistically significant higher HT prevalence of 47.6% compared to 33.7% in females (p<0.0001). CONCLUSION: Hyperlipedimia is reaching higher prevalence rates in KSA. This finding may suggest that CAD will soon be a major health problem. Reduction in obesity by adopting healthier eating habits, and increasing physical activity are of considerable importance to our community.

Prevalence of physical activity and inactivity among Saudis aged 30-70 years. A population-based cross-sectional study.

OBJECTIVE: To assess physical activity levels among Saudi adults, and to examine the relationships of physical activity with body mass index (BMI), waist circumference (WC) and obesity prevalence. METHODS: Data taken from the Coronary Artery Disease in Saudis Study which is a National Epidemiological Health Survey carried out between 1995 and 2000. Participants included 17395 Saudi males and females aged 30-70 years, selected randomly using a multistage stratified cluster sampling technique. Leisure-type and sport-related physical activities including walking were assessed using an interviewed-administered questionnaire. The activities were classified into five intensity categories and assigned metabolic equivalents (MET) according to the compendium of physical activity. Based on the intensity, duration and frequency of physical activity, subjects were classified into active or inactive category. RESULTS: Inactivity prevalence (96.1%) was very high. There were significantly (p<0.001)) more inactive females (98.1%) than males (93.9%). Inactivity prevalence increases with increasing age category, especially in males, and decreases with increasing education levels. Inactivity was the highest in the central region (97.3%; 95% CI = 96.8-97.8%) and the lowest in the southern region of Saudi Arabia (94.0%; 95% CI = 93.2-94.8%). Further, active individuals exhibited lower values of BMI and WC. CONCLUSION: These findings reveal the sedentary nature of Saudi population. The overwhelming majority of men and women did not reach the recommended physical activity levels necessary for promoting health and preventing diseases. The high prevalence of inactivity among Saudis represents a major public health concern.

Hypertension in Saudi Arabia.

OBJECTIVE: To determine the prevalence of hypertension among Saudis of both gender, between the ages of 30-70 years in rural as well as urban communities. This work is part of a major national study on Coronary Artery Disease in Saudis Study (CADISS). METHODS: This is a community-based study conducted by examining subjects in the age group of 30-70 years of selected households during a 5-year period between 1995 and 2000 in Saudi Arabia. Data were obtained from history using a validated questionnaire, and examination including measurement of blood pressure. The data were analyzed to provide prevalence of hypertension. Logistic regression was used to develop a risk assessment model for prevalence of hypertension. RESULTS: The total number of subjects included in the study was 17,230. The prevalence of hypertension was 26.1% in crude terms. For males, the prevalence of hypertension was 28.6%, while for females; the prevalence was significantly lower at 23.9% (p<0.001). The urban population showed significantly higher prevalence of hypertension of 27.9%, compared to rural population's prevalence of 22.4% (p<0.001). The prevalence of CAD among hypertensive patients was 8.2%, and 4.5% among normotensive subjects (p<0.001). Increasing weight showed significant increase in prevalence of hypertension in a linear relationship. CONCLUSION: Hypertension is increasing in prevalence in KSA affecting more than one fourth of the adult Saudi population. We recommend aggressive management of hypertension as well as screening of adults for hypertension early to prevent its damaging consequences if left untreated. Public health awareness of simple measures, such as low salt diet, exercise, and avoiding obesity, to maintain normal arterial blood pressure need to be implemented by health care providers.

Metabolic syndrome in Saudi Arabia.

OBJECTIVES: Metabolic syndrome (MS) is a well-established risk factor for the development of coronary artery disease (CAD). We designed this study to obtain the prevalence of MS and each of its components in Saudi Arabia. This study is part of Coronary Artery Disease in Saudi Study (CADISS). METHODS: We conducted this community-based national epidemiological health survey by examining Saudi subjects in the age group of 30-70 years of selected households over a 5-year period between 1995 and 2000 in Saudi Arabia. We interviewed all subjects, examined and took measurements of their blood pressure, weight, height, waist circumference, as well as fasting samples of plasma glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol. We obtained the prevalence of MS based on the presence of at least 3 of the following: abdominal obesity (waist circumference > 102 cm (40 inch) in male and > 88 cm (35 inch) in female), triglycerides > or = 150 mg/dl (1.69 mmol/L), HDL cholesterol < 40 mg/dl (1.03 mmol/L) in male and < 50 mg/dl (1.29 mmol/L) in female, blood pressure > or = 130/85 mm Hg, fasting glucose > or = 110 mg/dl (6.1 mmol/L) as defined by the Adult Treatment Panel (ATP) III in 2001. RESULTS: We included 17,293 subjects in this survey during the study period. The overall age-adjusted prevalence of MS in Saudi Arabia obtained from this study is 39.3%. Age adjusted prevalence in males is 37.2% and crude prevalence is 40.9% (95% confidence interval [CI] 39.8-42), while females have a higher prevalence of 42% and crude prevalence of 41.9% (95% CI 40.9-42.9). Saudi subjects from urban areas have significantly higher prevalence of 44.1% (95% CI 43.2-45) compared to those living in rural areas of 35.6% (95% CI 34.3-36.7) (p<0.0001). Low HDL affects 81.8% of females and 74.8% of males with MS leading all other factors, and it continued to be consistent in all different age groups. Metabolic syndrome is a risk factor for CAD, as the prevalence of CAD was higher among patients with MS (6.7%) compared to subjects without MS (4.6%) (p<0.0001). CONCLUSION: The prevalence of MS is high in Saudi Arabia. Low HDL cholesterol plays a major role in the contribution to the MS in Saudi Arabia. Therefore, we recommend routine assessment for the components of MS in patients with CAD, furthermore, we encourage aggressive management of the MS for primary prevention of CAD, particularly, measures to increase HDL cholesterol.

Tissue factor pathway inhibitor, natural coagulation inhibitors and hemostatic activation markers in patients with acute coronary syndromes.

OBJECTIVE: This study aims at characterizing the hemostatic changes, in a large cohort of Saudi Arab patients with acute coronary syndromes. METHODS: We consecutively enrolled 389 patients (unstable angina [UA]: n=181; myocardial infarction [MI]: n=208) in this study at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia in the period from April 2000 to November 2001. We collected blood samples before coronary angiography. Controls (n=101) were healthy males and females. All hemostatic assays were undertaken using enzyme linked immunosorbent assay based techniques and commercial kits. RESULTS: The mean plasma levels of both bound and free tissue factor pathway inhibitors (TFPI) were significantly higher and to comparable levels, in patients with MI and UA, than in healthy control levels. Markers of thrombin generation: the mean levels of prothrombin fraction 1+2, thrombin antithrombin complexes, and D-Dimer were very significantly elevated in the 2 patients groups than in controls. Proteins C and antithrombin III showed statistically significant reduction especially in patients with MI. Plasminogen activator inhibitor levels were significantly elevated in the 2 patient groups, but were higher in MI patients. The mean levels of fibrinogen and D-Dimer as well thrombin antithrombin complex were higher and the levels of free tissue factor pathway inhibitor were lower in patients with 3-vessel coronary artery disease than those with single and double vessel disease. CONCLUSION: The results of this study confirm the existence, and to a similar extent, of a hypercoagulable state in Saudi patients with MI than UA and in those with 3-vessel coronary artery disease than those with one or 2-vessel disease.

Obesity in Saudi Arabia.

OBJECTIVE: Obesity and overweight are well known risk factors for coronary artery disease (CAD), and are expected to be increasing in the Kingdom of Saudi Arabia (KSA) particularly among females. Therefore, we designed this study with the objective to determine the prevalence of obesity and overweight among Saudis of both gender, between the ages of 30-70 years in rural as well as in urban communities. This work is part of a major national project called Coronary Artery Disease in Saudis Study (CADISS) that is designed to look at CAD and its risk factors in Saudi population. METHODS: This study is a community-based national epidemiological health survey, conducted by examining Saudi subjects in the age group of 30-70 years of selected households over a 5-year period between 1995 and 2000 in KSA. Data were obtained from body mass index (BMI) and were analyzed to classify individuals with overweight (BMI = 25-29.9 kg/m2), obesity (BMI >/=30 kg/m2) and severe (gross) obesity (BMI >/=40 kg/m2) to provide the prevalence of overweight and obesity in KSA. RESULTS: Data were obtained by examining 17,232 Saudi subjects from selected households who participated in the study. The prevalence of overweight was 36.9%. Overweight is significantly more prevalent in males (42.4%) compared to 31.8% of females (p<0.0001). The age-adjusted prevalence of obesity was 35.5% in KSA with an overall prevalence of 35.6% [95% CI: 34.9-36.3], while severe (gross) obesity was 3.2%. Females are significantly more obese with a prevalence of 44% than males 26.4% (p<0.0001). CONCLUSION: Obesity and overweight are increasing in KSA with an overall obesity prevalence of 35.5%. Reduction in overweight and obesity are of considerable importance to public health. Therefore, we recommend a national obesity prevention program at community level to be implemented sooner to promote leaner and consequently healthier community.

Diabetes mellitus in Saudi Arabia.

OBJECTIVE: Diabetes mellitus (DM) is a major public health problem worldwide, and it is a known risk factor for coronary artery disease (CAD). New recommendations for the diagnosis of diabetes have changed the epidemiology of DM. Therefore, we designed this study with the objective to determine the prevalence of DM among Saudis of both sexes, between the ages of 30-70-years in rural as well as urban communities. This work is part of a major national project: Coronary Artery Disease in Saudis study (CADISS) that is designed to look at CAD and its risk factors in Saudi population. METHODS: This study is a community-based national epidemiological health survey, conducted by examining Saudi subjects in the age group of 30-70-years of selected households over a 5-year period between 1995 and 2000. Data were obtained from history, fasting plasma glucose levels, and body mass index. The data were analyzed to classify individuals as diabetic, impaired fasting glucose and normal, using 1997 American Diabetes Association (ADA) criteria, which was adopted by the World Health Organization (WHO) in 1998, to provide prevalence of DM in the Kingdom of Saudi Arabia (KSA). RESULTS: A total of 17232 Saudi subjects were selected in the study, and 16917 participated (98.2% response rate). Four thousand and four subjects (23.7%), out of 16917 were diagnosed to have DM. Thus, the overall prevalence of DM obtained from this study is 23.7% in KSA. The prevalence in males and females were 26.2% and 21.5% (p<0.00001). The calculated age-adjusted prevalence for Saudi population for the year 2000 is 21.9%. Diabetes mellitus was more prevalent among Saudis living in urban areas of 25.5% compared to rural Saudis of 19.5% (p<0.00001). Despite the readily available access to healthcare facilities in KSA, a large number of diabetics 1116 (27.9%) were unaware of having DM. CONCLUSION: The overall prevalence of DM in adults in KSA is 23.7%. A national prevention program at community level targeting high risk groups should be implemented sooner to prevent DM. We further recommend a longitudinal study to demonstrate the importance of modifying risk factors for the development of DM and reducing its prevalence in KSA.