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T C Theoharides

Publications and source records attributed to T C Theoharides.

141 records · Page 8Linked to original sources
PubMedDate not supplied

Conjugated linoleic acid: a functional food?

Scientific interest in conjugated linoleic acid (CLA) started in 1987 when Michael Pariza's team of Wisconsin University observed its inhibitory effects on chemically induced skin tumors in mice. Numerous studies have since examined CLA's role in cancer, immune function, oxidative stress, atherosclerosis, lipid and fatty acids metabolism, bone formation and composition, obesity, and diabetes. Still it's not clear yet either through which mechanisms CLA produces its numerous metabolic effects. We now know that CLA contents in cow milk fat can be enriched through dry fractionation, but this knowledge doesn't allow sufficient certainty to qualify this nutrient, as a functional food, capable of increasing well being and reducing the risk of disease.

Animals↗
PubMedDate not supplied

A pilot open label study of Cystoprotek in interstitial cystitis.

Interstitial cystitis (IC) is a disorder of the urinary bladder characterized by urgency, frequency, nocturia and suprapubic pain. IC occurs primarily in women and symptoms are exacerbated by stress, ovulatory hormones and certain foods. IC pathogenesis is unknown, but the most consistent findings involve some dysfunction of the bladder glycosaminoglycan (GAG) protective layer and a high number of activated bladder mast cells. There is no effective therapy even through intravesical administration of dimethylsulfoxide (DMSO) or oral pentosanpolysulfate (PPS) have had variable success. A dietary supplement, CystoProtek, was formulated with the natural GAG components chondroitin sulfate and sodium hyaluronate to provide urothelial cytoprotection, together with the flavonoid quercetin that has anti-inflammatory properties and inhibits activation of mast cells. Thirty-seven female patients diagnosed by the NIDDK criteria who had failed all forms of therapy took six softgel CystoProtek capsules per day for 6 months. Global assessment scale was reduced from 9.0 +/- 2.9 to 4.3 +/- 2.1 (p < 0.05); moreover, the O'Leary/Sant Symptom Index decreased from 15.3 +/- 3.1 to 6.9 +/- 4.2 (p < 0.05) and the Problem Index from 13.1 +/- 3.7 to 5.4 +/- 4.0 (p <0.05). These results are very promising and warrant a larger study that may permit further analyses with respect to other, especially atopic, comorbid diseases.

Adult↗
PubMedDate not supplied

Mesenteric traction syndrome or gut in distress.

The mesenteric traction syndrome (MTS) remains, seventeen years after its first designation as a distinct pathologic entity, an aspect of surgical practice that has received limited attention. Apart from its symptomatology, there is mostly speculation about its exact causes and pathophysiologic mechanisms. Even though full-blown MTS is rather rare, the advent of laparoscopic surgery has indicated that there are different stages of stress associated with open abdominal surgery. Some evidence points to the involvement of mast cell derived vasoactive mediators and suggests possible pharmacologic management.

Flushing↗
PubMedDate not supplied

Theophylline as "add-on" therapy in patients with delayed pressure urticaria: a prospective self-controlled study.

Delayed pressure urticaria (DPU) is a skin condition that involves the gradual development of wheals and edema at sites of physical pressure. Its pathogenesis is not clear and histamine-1 receptor (H-1R) antagonists provide only partial relief. In this prospective, clinical study, we investigated the effect of theophylline, which has a long history of benefit in allergic asthma, added to cetirizine in patients with DPU. Twenty three patients received during period 1 cetirizine (10 mg po QD) and theophylline (200 mg po BID) for 6 months, followed by period 2 of 1 month washout with only rescue medication as needed, and then by period 3 with cetirizine (10 mg QD plus placebo (BID) for 5 more months. The addition of theophylline resulted in statistically significant improvement over cetirizine alone by 2 months and continued for the duration of treatment. Treatment of cultured human mast cells with theophylline (10 microM) did not inhibit allergic histamine release, but the in vivo beneficial effect of theophylline may require significant pretreatment period to manifest itself, or may involve inhibition of other mast cell dependent mediators. A double-blind study, accompanied by serum histamine and tryptase levels, should be in order.

Adult↗
PubMedDate not supplied

A pilot, open label, clinical trial using hydroxyzine in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder of myelin destruction. Blood-brain-barrier (BBB) disruption precedes pathological or clinical findings and could involve mediators from perivascular brain mast cells, such as histamine and vascular endothelial growth factor (VEGF). Mast cells could be activated by many triggers, including acute stress that has been correlated with MS exacerbations. We considered that the histamine-1 (H1) receptor antagonist hydroxyzine, which also partially inhibits brain mast cells and has anxiolytic properties, may reduce MS symptoms. This open label, pilot, clinical trial investigated the effect on MS of an oral solution of hydroxyzine (100 mg per day), together with caffeine (200 mg per day) to reduce sedation. Twenty patients (8 males; 12 females) with relapsing-remitting or relapsing-progressive MS completed the study (12 +/- 1 months) and were evaluated using disability scales. Most patients on hydroxyzine (75%) remained stable or improved neurologically and all but one showed improved mood. Hydroxyzine could be used as an adjuvant in MS, but the small number of patients enrolled and the short duration of the study precludes any definitive conclusions. A double-blind, placebo-controlled study is warranted.

Adolescent↗
PubMedDate not supplied

Progesterone inhibits mast cell secretion.

Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.

Animals↗
PubMedDate not supplied

Anti-inflammatory actions of flavonoids and structural requirements for new design.

Flavonoids are low molecular weight compounds rich in seeds, citrus fruits, olive oil, tea and red wine, with potent antioxidant, cytoprotective and antiinflammatory activities. Flavonoids are composed of a three-ring structure (A,B and C) with various substitutions; they can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3 or a hydroxyl group in position 3 of the C (middle) ring. Particular hydroxylation patterns of the B ring of the flavones permit them to inhibit histamine, tryptase, interleukin-6 and interleukin-8 release from human umbilical-cord derived cultured mast cells, as well as from macrophages. The catechol (o-dihydroxy) group in the B ring as in quercetin confers potent inhibitory ability, while a pyrogallol (trihydroxy) group, as in myricetin, produces even higher activity. However, addition of one hydroxyl group on position 2&#x2032; of the B ring, as in the flavonol morin, renders this compound inactive. The C2-C3 double bond of the C ring appears to increase scavenger activity because it confers stability to the phenoxy-radicals produced, while the 4-oxo (keto double bond at position 4 of the C ring) increases free radical scavenger activity by delocalizing electrons from the B ring. The 3-OH group on the C ring appears tobe critical for anti-inflammatory activity. Inhibition of mast cell secretion was shown to be mediated by a 78-kD phosphoprotein which has been cloned and serves as a bridge between the cell surface and the cytoskeleton. Phosphorylation at particular sites in the C-terminus unfolds the three dimensional structure of this protein making actin binding sites accessible; crosslinking with actin in the cytoskeleton prevents secretion of inflammatory mediators. These properties present unique opportunities for the synthesis of new compounds for the treatment of inflammatory and possibly proliferative disorders.

Journal Article↗
PubMedDate not supplied

Increased expression of intercellular adhesion molecule 1 in relation to mast cells in the bladder of interstitial cystitis patients.

Interstitial cystitis (IC) is a sterile, painful bladder disorder, often associated with inflammation. A defective urothelium and activated mast cells have been implicated in the pathophysiology of IC. Mast cells have been reported to induce the expression of intercellular adhesion molecules (ICAM) that are considered a necessary first step for the initiation of inflammation. We investigated the presence of ICAM-1 and its association with bladder mast cells in IC patients and controls in order to further understand their role in the pathophysiology of IC. Bladder tissue was fresh frozen and 7m section were cut using a cryostat. Immunocytochemical detection was carried out with monoclonal antibodies directed against anti-ICAM1 and tryptase. Twenty-one biopsies from women with IC and two from normal tissue from radical cystectomies (control) were analyzed. All IC samples were strongly positive for ICAM-1, exclusively in capillaries. Control samples were only faintly positive in fewer capillaries. Numerous mast cells were identified in the positive regions with toluidine blue or tryptase immunocytochemistry. This work may help explain why many IC patients develop sterile inflammation. It may also provide evidence further explaining the role of bladder mast cells in the pathophysiology of IC.

Journal Article↗
PubMedDate not supplied

Effect of stress and other psychological factors on the pathophysiology and treatment of dermatoses.

Psychological factors precipitate or increase the morbidity of many dermatoses. There is increasing evidence that stress influences disease processes and contributes to the inflammation through vasoactive neuropeptides, lymphokines or other chemical mediators. Experimental results indicate that the endocrine, nervous and immune systems can no longer be considered autonomous, but involve complex bidirectional interactions between them. Dermatology holds a distinct position in psychosomatic medicine because it deals with an organ that can be readily seen and touched. The psychological states of anxiety, fear, shame, pleasure, and sexual excitation are visibly indicated by blushing, hair-rising, growing pale, itching or hyperhidrosis. The skin, therefore, clearly responds to many psychologic and stressful stimuli. As the skin is exposed to view, dermatoses elicit reactions from the patients' environment and the easy accessibility of the skin allows patients to interact directly with their lesions. In addition to the classic stress response involving increased levels of neuroendocrine hormones and autonomic neurotransmitters, stress also affects the immune system. Stress has been reported to cause decreased natural killer cell cytotoxicity, depressed mitogenic responses in lymphocytes, increased IgA levels, enhanced neutrophil phagocytosis and activation of interferon synthesis in lymphocytes. Psychodermatological syndromes can be classified according to the type and degree of causal relationship between the psychological etiology and the dermatoses. There is some overlap between the groups, but there is a satisfactory classification under three major headings that suggests an approach to treatment.

Journal Article↗
PubMedDate not supplied

Fibromyalgia--new concepts of pathogenesis and treatment.

Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.

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