Glycerol Handling in Paired Visceral and Subcutaneous Adipose Tissues in Women with Normal Weight and Upper-Body Obesity.

In adipose tissue, reduced expression of the glycerol channel aquaporin 7 (AQP7) has been associated with increased accumulation of triglyceride. The present study determines the relative protein abundances of lipolytic enzymes, AQP7, and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in paired mesenteric and omental visceral adipose tissue (VAT) and abdominal and femoral subcutaneous adipose tissue (SAT) in women with either normal weight or upper-body obesity. No differences in the expression of hormone-sensitive lipase (HSL) or AQP7 were found between the two groups in the four depots.

Thermodynamic characterization of new positive allosteric modulators binding to the glutamate receptor A2 ligand-binding domain: combining experimental and computational methods unravels differences in driving forces.

Positive allosteric modulation of the ionotropic glutamate receptor GluA2 presents a potential treatment of cognitive disorders, for example, Alzheimer's disease. In the present study, we describe the synthesis, pharmacology, and thermodynamic studies of a series of monofluoro-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides. Measurements of ligand binding by isothermal titration calorimetry (ITC) showed similar binding affinities for the modulator series at the GluA2 LBD but differences in the thermodynamic driving forces.

Positive allosteric modulators of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid receptors belonging to 4-cyclopropyl-3,4-dihydro-2h-1,2,4-pyridothiadiazine dioxides and diversely chloro-substituted 4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides.

Two 4-ethyl-substituted pyridothiadiazine dioxides belonging to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators were cocrystallized with the GluA2 ligand binding domain in order to decipher the impact of the position of the nitrogen atom on their binding mode at the AMPA receptors. The latter was found to be very similar to that of previously described benzothiadiazine-type AMPA receptor modulators. The affinity of the two compounds for the receptor was determined by isothermal titration calorimetry.

Synthesis, pharmacological and structural characterization, and thermodynamic aspects of GluA2-positive allosteric modulators with a 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide scaffold.

Positive allosteric modulators of ionotropic glutamate receptors are potential compounds for treatment of cognitive disorders, e.g., Alzheimer's disease.

The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking.

Intrinsic disorder is important for protein regulation, yet its role in regulation of ion transport proteins is essentially uninvestigated. The ubiquitous plasma membrane carrier protein Na(+)/H(+) Exchanger isoform 1 (NHE1) plays pivotal roles in cellular pH and volume homeostasis, and its dysfunction is implicated in several clinically important diseases. This study shows, for the first time for any carrier protein, that the distal part of the C-terminal intracellular tail (the cdt, residues V686-Q815) from human (h) NHE1 is intrinsically disordered.

Temperature-dependent structural changes in intrinsically disordered proteins: formation of alpha-helices or loss of polyproline II?

Structural characterization of intrinsically disordered proteins (IDPs) is mandatory for deciphering their potential unique physical and biological properties. A large number of circular dichroism (CD) studies have demonstrated that a structural change takes place in IDPs with increasing temperature, which most likely reflects formation of transient alpha-helices or loss of polyproline II (PPII) content. Using three IDPs, ACTR, NHE1, and Spd1, we show that the temperature-induced structural change is common among IDPs and is accompanied by a contraction of the conformational ensemble.

Dietary restrictions in the treatment of adult patients with eczema.

Improvement was seen in the dermatitis of 262 of 675 patients who followed a restrictive diet for approximately 1 month. Patients included in the study were sensitive to metal salts, balsams or classical food allergens or reacted to oral challenge with food additives. Also included were patients who did not react to diagnostic tests but who experienced improvement of their dermatitis while maintaining an elimination diet.

Oral challenge with food additives.

A randomized, placebo-controlled oral challenge with food additives (preservatives and food colorings) was carried out in 101 patients with eczema of undetermined origin who suspected that the intake of certain foods aggravated their dermatitis. 37 reacted to 1 or more of the food additives but not to a placebo, while 16 reacted to the placebo, or both the placebo and food additives. 48 had no reactions.

Oral challenge with nickel and cobalt in patients with positive patch tests to nickel and/or cobalt.

During a 3-year period, 146 patients with positive patch tests to nickel and/or cobalt, for whom a systemic cause of dermatitis was suspected, were challenged orally with a single dose of 2.5 mg nickel given as nickel sulphate and 1 mg cobalt given as cobalt sulphate using a double-blind, placebo-controlled method. No following-up was possible for 2 patients.

Dermatitis induced or aggravated by selected foodstuffs.

The eczema of 113 patients with dermatitis other than classical urticaria or typical atopic dermatitis cleared or showed marked improvement after one to two months of dietary restriction. In their response to a questionnaire completed at least 6 months after the initiation of the diet, 61 (54%) of these patients said that diet restriction was effective in reducing the activity of or preventing recurrence of their dermatitis. Their most common symptoms were recurrent symmetrical hand eczema, anogenital eczema, pruritic papules and excoriations of the trunk as well as a "fixed" type of eczema.

Aluminium allergy.

13 children ranging in age from 1 to 13 years and 1 adult patient had positive patch tests to 2% AlCl3 in water. 13 of them had pruritic excoriated papules, 9 at sites of hyposensitization therapy with aluminium-bound pollen extracts, and 4 at sites of childhood immunization with an aluminium-bound vaccine (Di-Te-Pol). For the 1 adult patient, the positive patch test was not considered to be of current relevance.

Reduction of intake of balsams in patients sensitive to balsam of Peru.

64 patients participated in this study. 24 were patients who had positive patch tests to balsam of Peru. The dermatitis of 9 of the patients had flared after open oral challenge with balsam of Peru, and the dermatitis of 31 patients had flared after double-blind oral challenge.

Dietary treatment of nickel dermatitis.

During a 5-year period, 61 patch-test-negative patients whose dermatitis flared after oral challenge with 2.5 mg nickel and 143 patients with positive patch tests to nickel who were not challenged orally adhered to a diet intended to reduce the daily intake of nickel for at least one month. After 1 to 2 months of dieting the dermatitis in 121 of the 204 patients had cleared or was markedly improved.

Hydrocortisone 17-butyrate (Locoid) 0.1% cream versus hydrocortisone (Uniderm) 1% cream in the treatment of children suffering from atopic dermatitis.

A randomized, double-blind, left-right study to compare the therapeutic efficacy of hydrocortisone 17-butyrate (Locoid) 0.1% cream with hydrocortisone (Uniderm) 1% cream was performed in forty children suffering from atopic dermatitis. The medications were applied to symmetrical bilateral skin lesions twice daily for a maximum of 4 weeks or until complete clinical clearance of such lesions had occurred.

Oral challenge with metal salts. (II). Various types of eczema.

299 patients with chronic dermatitis of obscure origin were challenged orally in a controlled study with 2.5 mg nickel, 2.5 mg chromium, and 1 mg cobalt given as salts of the respective metals.

Oral challenge with metal salts. (I). Vesicular patch-test-negative hand eczema.

202 patients, 68 males and 134 females, with patch-test-negative, symmetrical vesicular hand eczema were challenged orally in a controlled study with 2.5 mg nickel, 2.5 mg chromium and 1 mg cobalt given as salts of the respective metals.

Patch testing with substances not included in the standard series.

During a 5-year period, 3664 consecutive patients were patch tested in a private dermatology practice with the Standard Series of the International Contact Dermatitis Research Group (ICDRG). 454 of these were tested with one or more additional substances which were suspected of having caused their dermatitis. 194 of the 454 patients had positive reactions to one or more of the additional substances.

Causes of eczema in the food industry.

In a retrospective study covering a five-year period, 3664 consecutive patients suspected to suffer from contact dermatitis were patch tested in a private dermatology clinic. 180 of these patients had food handling occupations; they were employed in restaurant or institutional kitchens, fish factories, bakeries, or slaughterhouses. 25 of the 180 patients had protein dermatitis caused by meat or vegetables.

Contact dermatitis in children.

168 children, 14 years of age or younger, were patch tested with the Standard Series of the International Contact Dermatitis Research Group (ICDRG) over a 5-year period. 77 of the children had 1 or more positive reactions; relevant test results were found in 80% of them. 8 boys and 24 girls were allergic to nickel, which proved to be the most common allergen; 5 boys and 6 girls reacted to chromate, and 5 boys and 4 girls reacted to one or more of the rubber chemicals.