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The combination of immunodeficiency, inflammatory process and nutritional status that is characteristic of infective and food-borne illness is more evident in chronic diet- and environment-influenced chronic diseases such as diabetes, obesity, cardiovascular disease, cancer, arthritis and neuro-degeneration diseases. These chronic diseases tend to be oxidation-linked and may manifest in communities around the world, irrespective of income. In addressing the challenges of the above diseases, a significant role for dietary phytochemicals is emerging. Phytochemicals are required from a spectrum of food for at least their antioxidant role, if not for other properties, to protect tissues from activities that manifest themselves into what we call chronic disease. Among the diverse groups of phytochemicals, phenolic antioxidants and antimicrobials from food plants are being targeted for designed dietary intervention to manage major oxidation-linked diseases such as diabetes, cardiovascular diseases, arthritis, cognition diseases and cancer. Foods containing phenolic phytochemicals are also being targeted to manage bacterial infections associated with chronic diseases such as peptic ulcer, urinary tract infections, dental caries and food-borne bacterial infections. Plants produce phenolic metabolites as a part of growth, developmental and stress adaptation response. These stress and developmental responses are being harnessed to design consistent phytochemical profiles for safety and clinical relevancy using novel tissue culture and bioprocessing technologies. The biochemical strategy for harnessing phenolic phytochemicals for human health and wellness is based on the hypothesis that phenolic metabolites in plants are efficiently produced through an alternative mode of metabolism linking proline synthesis with pentose-phosphate pathway. In this model, stress-induced proline biosynthesis is coupled to pentose-phosphate pathway, driving the synthesis of NADPH(2) and sugar phosphates for anabolic pathways, including phenolic and antioxidant response pathways, while simultaneously providing reducing equivalents needed for mitochondrial oxidative phosphorylation in the form of proline as an alternative to NADH from Krebs/TCA cycle. Based on this model, tissue culture techniques and elicitation concepts have been used to stimulate phenolic metabolites with an antioxidant response in germinating seeds, sprouts and clonal lines of dietary plants. From our initial investigations, a model has been proposed in which the proline-linked pentose-phosphate pathway is suggested to be critical for modulating protective antioxidant response pathways in diverse biological systems, including biochemical and cellular pathways important for human health. The proposed proline-linked pentose-phosphate pathway model provides a mechanism for understanding the mode of action of phenolic phytochemicals in modulating antioxidant pathways and provides avenues by which dietary approaches may manage oxidation-linked chronic and infectious diseases. The model also has implications for the development of antimicrobial phenolic phytochemicals against bacterial pathogens in an era of increasing antibiotic resistance. Further, this model also has relevance for improving fungal and yeast-based food bioprocessing for designing functional foods and for environmental bioremediation using plant and microbial systems, as well as for improving agricultural and food systems in harsh environments.
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PMID:A model for the role of the proline-linked pentose-phosphate pathway in phenolic phytochemical bio-synthesis and mechanism of action for human health and environmental applications. 1500 10

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders.
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PMID:Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders. 1552 86

Surgery for morbid obesity should be considered in case of failure of conservative treatment (diet, physical activity, psychotherapy, supportive medications). It is strongly recommended also for patients with significant concomitant diseases (e.g. cardiovascular, pulmonary etc) difficult to manage with traditional therapy. Patients' selection for surgery seems to be essential issue. Typical indications for surgical procedure include: BMI > 40 or BMI > 35 in patients with at least two obesity-related diseases, ineffective conservative treatment. Main contraindications are GI tract diseases (esophagitis, peptic ulcer), severe cardiovascular insufficiency, alcohol or drug abuse and mental disorders. There are two types of operative procedures currently performed restrictive and malabsorptive. The first group consists of following operations: 1) Silicon Ring Vertical Gastroplasty (SRVG), 2) Vertical Banded Gastroplasty (VBG), 3) Adjustable Silicon Gastric Banding (ASGB), 4) Non-Adjustable Gastric Banding (NGB). The latter group comprises: 1) Roux-Y Gastric By-Pass (RYGB) and 2) Bilipancreatic diversion. The paper describes complications, advantages and disadvantages for both groups of bariatric procedures and points out factors that should be considered in patients' selection for various types of operation.
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PMID:[Indications and contraindications for surgical treatment of morbid obesity--the choice of operative method]. 1560 67

This article reviews the development of our knowledge of the actions of histamine which have taken place during the course of the 20th century. Histamine has been shown to have a key physiological role in the control of gastric acid secretion and a pathophysiological role in a range of allergic disorders. The synthesis of, and pharmacological studies on, selective agonists and antagonists has established the existence of four types of histamine receptor and histamine receptor antagonists have found very important therapeutic applications. Thus, in the 1940s, H(1)-receptor antagonists ('the antihistamines') yielded and still provide valuable treatment for allergic conditions such as hay fever and rhinitis. In the late 1970s and 1980s, H(2)-receptor antagonists (in the discovery of which the two authors were personally involved) revolutionised the treatment of peptic ulcer and other gastric acid-related diseases. The H(3)-receptor antagonists, although available since 1987, have been slower to find a therapeutic role. However, the discovery of nonimidazole derivatives such as brain-penetrating H(3) antagonists has provided drugs that are in early-phase clinical trials, possibly for application in obesity, and a variety of central nervous system disorders, such as memory, learning deficits and epilepsy. Finally, the most recently (1999) discovered H(4) receptor promises the potential to provide drugs acting on the immunological system with possible applications in asthma and inflammation.
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PMID:Histamine and its receptors. 1640 96

The authors' aim in this study was to explore the prevalence, symptomatology, and risk factors for peptic ulcer in a general adult population. Between December 1998 and June 2001, the authors surveyed a random sample (n=3,000) of the adult population (n=21,610) in two communities in northern Sweden using a validated questionnaire, the Abdominal Symptom Questionnaire (response rate=74%). A subsample (n=1,001) of the responders was randomly invited to undergo esophagogastroduodenoscopy and symptom assessment (response rate=73%). The prevalence of peptic ulcer was 4.1% (20 gastric ulcers and 21 duodenal ulcers). Nausea and gastroesophageal reflux were significant predictors of peptic ulcer disease, but epigastric pain/discomfort was not. Six persons with gastric ulcer and two persons with duodenal ulcer were asymptomatic. Eight subjects with duodenal ulcer (38%) lacked evidence of current Helicobacter pylori infection. Five (25%) of the gastric ulcers and four (19%) of the duodenal ulcers were idiopathic (no use of aspirin or nonsteroidal antiinflammatory drugs, no H. pylori infection). Smoking, aspirin use, and obesity were risk factors for gastric ulcer; smoking, low-dose (<or=160 mg) aspirin use, and H. pylori infection were risk factors for duodenal ulcer. Peptic ulcer disease often coexists with atypical symptoms or no symptoms at all, and idiopathic duodenal ulcer may be more common than anticipated.
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PMID:Peptic ulcer disease in a general adult population: the Kalixanda study: a random population-based study. 1655 43

Our objective was to clarify how different groups of chronic morbidities are associated with indices of body composition, such as body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), skinfold index (SF), and fat-free mass index (FFMI). Our sample comprised Chuvasha residing in numerous villages in a rural area of the Russian Federation. The investigated cohort included 787 males aged 18-89 years, and 716 females aged 18-90 years. We performed a cross-sectional, community-based study of a large sample of individuals not receiving any medications for treatment or prevention of chronic morbidities. To elucidate the association between morbidity and age-adjusted anthropometrical indices, we used one-way analysis of variance, wherein the above indices were the dependent variables, while individuals affected vs. nonaffected for a specific disease were the grouping variables. Individuals with ischemic heart disease, diabetes mellitus, hypertension, and peptic ulcer showed significant differences in their BMI, WC, WHR, and SF. In the first diseases, mean values of anthropometric indices were higher in affected individuals, whereas in the peptic ulcer group, mean values were higher in the nonaffected. Skin diseases and gynecological diseases showed significant differences in WHR. Mean values in affected individuals were lower than in the nonaffected. The group afflicted with local forms of arthritis showed significant differences in FFMI, suggesting that arthritis is not linked to obesity, but is linked to high lean mass. Rheumatic diseases positively correlated with WC and FFMI.
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PMID:Indices of body composition and chronic morbidity: a cross-sectional study of a rural population in central Russia. 1663 21

Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty. Gout results from the body's reaction to urate crystals deposited in tissues, and this pathophysiology is well understood. If used appropriately, available therapies can be entirely effective in not only treating the symptoms of gout, but also in eliminating the excess urate from the body, thereby eradicating the disease. Because of these facts, management of patients with gout should be successful. However, management of gout is particularly challenging in the elderly, even though the principles of management are the same for all age groups. The purpose of this article is to review these principles and discuss them as they pertain to the elderly. The classic gout attack is acute in onset, extremely painful and associated with marked swelling, warmth, erythema and tenderness of a single joint. However, the diagnosis of gout may be challenging in the elderly because atypical presentations are more common in this group. Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid conditions such as chronic kidney disease, peptic ulcer disease and congestive heart failure may make the use of these agents dangerous or contraindicated. Thus, it is important to try to treat an acute flare of gout at the earliest sign, because the sooner treatment is initiated, the faster the inflammation will resolve. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used judiciously in the elderly. However, if used at the lowest dose that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the body will be eliminated, acute flares will no longer occur and tophi will resolve. Gout is often seen in association with hypertension, excessive alcohol consumption, obesity and hypertriglyceridaemia. These conditions and the medications used to treat them may contribute to the hyperuricaemia. Treating these conditions and using medications that do not promote hyperuricaemia will aid in the management of gout. Despite the challenges that often complicate the management of gout in the elderly, an understanding of the pathophysiology of the disease and both the indications and limitations of the medications used should allow successful treatment.
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PMID:Management of gout in older adults: barriers to optimal control. 1723 45

The new millennium has seen distinct changes in the pattern of gastrointestinal disease in the Asia-Pacific region. These changes are important as more than half of the world's population come from the region and therefore impact significantly on the global disease burden. The highest incidence of gastric cancer (GCA) has been reported from Asia and GCA remains a very important cancer. However time-trend studies have shown a decrease in GCA incidence in several countries in Asia. A rise in cardio-esophageal cancers as seen in the West has not been reported. On the other hand, colorectal cancer has been steadily increasing in Asia with age-standardized incidence rates of some countries approaching that of the West. The pattern of acid-related diseases has also changed. Gastroesophageal reflux disease is a fast emerging disease with an increasing prevalence of reflux esophagitis and reflux symptoms. The prevalence of peptic ulcer disease has at the same time declined in step with a decrease in H. pylori infection. Many of the changes taking place mirror the Western experience of several decades ago. Astute observation of the epidemiology of emerging diseases combined with good scientific work will allow a clearer understanding of the key processes underlying these changes. With rapid modernization, lifestyle changes have been blamed for an increase in several diseases including gastroesophageal reflux disease, nonalcoholic fatty liver disease and colorectal cancer. A worrying trend has been the increase in obesity among Asians, which has been associated with an increase in metabolic diseases and various gastrointestinal cancers. Conversely, an improvement in living conditions has been closely linked to the decrease in GCA and H. pylori prevalence.
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PMID:Changing trends in gastrointestinal disease in the Asia-Pacific region. 1797 Aug 73

The objective of this study was to evaluate comorbidity and risk factors associated with female urinary incontinence and to assess quality of life for women with different types of urinary incontinence. Subjects included 551 consecutive females who attended the outpatient clinic from 9 March to 8 July 2006 and did not have a chief complaint of incontinence. A four-item incontinence questionnaire and a Chinese version of the Incontinence-Quality of Life (I-QOL) questionnaire were completed in the waiting room. Patient characteristics and medical conditions were summarized from outpatient electronic databases. A total of 371 females were included for statistical analysis. Among them, 114 patients (30.7%) did not indicate any urinary incontinence, while 257 (69.3%) patients indicated symptoms of urge incontinence, stress incontinence, or mixed incontinence. Comorbidities significantly associated with incontinence included osteoarthritis (P = 0.001), peptic ulcer disease (P = 0.031), obesity (P < 0.001), and cardiac disease (P < 0.001). After multiple logistic regression analysis, obesity (OR 3.38, 95% CI 1.94-6.98) and postmenstrual status (OR 2.17, 95% CI 1.35-3.50) were found to be risk factors of incontinence (P < 0.001). Mixed incontinence patients exhibited the least satisfaction in quality of life, while no significant differences were observed between patients with urge incontinence and stress incontinence. In conclusion, the incidence of urinary incontinence may be greater in the outpatient population than previously thought. Osteoarthritis, peptic ulcer disease, and cardiac disease are more common in women with urinary incontinence, obesity and postmenopausal status appear predictive of incontinence, and women with mixed incontinence exhibit the least satisfying quality of life.
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PMID:Urinary incontinence among Taiwanese women: an outpatient study of prevalence, comorbidity, risk factors, and quality of life. 1919 71

We reviewed articles on the epidemiology and clinical characteristics of gastroesophageal reflux disease (GERD) in Japan to clarify these features of GERD in this country. Although the definition of GERD depends on the individual study, the prevalence of GERD has been increasing since the end of the 1990s. The reasons for the increase in the prevalence of GERD may be due to increases in gastric acid secretion, a decrease in the Helicobacter pylori infection rate, more attention being paid to GERD, and advances in the concept of GERD. More than half of GERD patients had non-erosive reflux disease, and the majority (87%) of erosive esophagitis was mild type, such as Los Angeles classification grade A and grade B. There were several identified risk factors, such as older age, obesity, and hiatal hernia. In particular, mild gastric atrophy and absence of H. pylori infection influence the characteristics of GERD in the Japanese population. We also discuss GERD in the elderly; asymptomatic GERD; the natural history of GERD; and associations between GERD and peptic ulcer disease and H. pylori eradication. We examined the prevalence of GERD in patients with specific diseases, and found a higher prevalence of GERD, compared with that in the general population, in patients with diabetes mellitus, those with obstructive sleep apnea syndrome, and those with bronchial asthma. We provide a comprehensive review of GERD in the Japanese population and raise several clinical issues.
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PMID:Epidemiology and clinical characteristics of GERD in the Japanese population. 1936


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