Dimeric Proanthocyanidins on the Stability of Dentin and Adhesive Biointerfaces.

A dentin biomodification strategy with selective proanthocyanidin (PAC)-enriched extracts reinforces dentin and dentin-resin interfaces. Enrichment of the extracts according to the degree of polymerization allows exploration of bioactive principles of PACs and structure-activity relationships. This study investigated the sustained dentin matrix biomodification and dentin-resin bioadhesion of 2 fractions consisting exclusively of B-type PAC dimers with or without a single galloyl motif (specifically, DIMERG and DIMERNG) and their precursor material, enriched grape seed extract (e-GSE; Vitis vinifera). The biomodification potential was determined by long-term evaluation of the apparent modulus of elasticity and collagen solubility (hydroxyproline release). Chemical characterization of the dentin matrix was performed by attenuated total reflectance-Fourier-transform infrared spectroscopy. The bioadhesive properties were assessed by a microtensile bond strength test at different time points, and macro-hybrid layers were produced to verify the degree of conversion of the adhesive resin. Fractions consisting of DIMERG, DIMERNG, and their precursor, e-GSE, increased the modulus of elasticity at all time points and reduced collagen degradation. Specimens treated with DIMERNG remained stable throughout 12 mo of storage, whereas a significant drop in the modulus of elasticity was observed for the DIMERG and e-GSE groups at 6 mo. The fractions and precursor did not affect the degree of resin conversion at the hybrid layer. Changes in infrared resonances corresponding to collagen cross-links in the dentin matrix occurred for all treatments. Higher bond strength was observed for dentin treated with e-GSE as compared with DIMERG and DIMERNG; all biointerfaces remained stable after 12 mo. Nongalloylated PACs mediate stable dentin biomodification, which includes protective activity against collagen degradation and reinforcement of the anchoring dentin matrix. Collectively, PACs with a higher degree of oligomerization offer a robust bioadhesion between the hydrophilic dentin matrix and the hydrophobic adhesive.

Biostability of the Proanthocyanidins-Dentin Complex and Adhesion Studies.

Oligomeric proanthocyanidins (OPACs) are potent and renewable natural bioactives possible to be refined into chemically standardized mixtures for biological applications. Herein, we found that multiscale interactions of OPACs with the dentin matrix create tight biointerfaces with hydrophobic methacrylate adhesives on wet surfaces. An enriched mixture of OPACs, with a known phytochemical profile, was produced from grape seed crude extract ( Vitis vinifera; enriched grape seed extract [e-GSE]) and applied to dentin matrices to determine changes to the mechanical properties and biodegradability of the dentin matrix and favorable resin adhesion mechanisms. Methods included a 3-point flexural test, quantification of hydroxyproline (collagen solubilization), static and dynamic nanomechanical analyses, resin-dentin microtensile bond strength, and micropermeability at the adhesive interface. The e-GSE-modified dentin matrix exhibited remarkably low collagen solubilization and sustained the bulk elastic properties over 12 mo. Tan δ findings reveal a more elastic-like behavior of the e-GSE-modified dentin matrix, which was not affected by H-bond destabilization by urea. Dentin-methacrylate biointerfaces with robust and stable adhesion were created on e-GSE-primed dentin surfaces, leading to a dramatic decrease of the interfacial permeability. Standardized OPAC mixtures provide a new mechanism of adhesion to type I collagen-rich tissues that does not rely on hydrophilic monomers. The bioadhesion mechanism involves physicochemical modifications to the dentin matrix, reduced tissue biodegradation, and bridging to methacrylate resins.

Effect of Bioactive Primers on Bacterial-Induced Secondary Caries at the Tooth-Resin Interface.

Secondary caries at the tooth-resin interface is the primary reason for replacement of resin composite restorations. The tooth-resin interface is formed by the interlocking of resin material with hydroxyapatite crystals in enamel and collagen mesh structure in dentin. Efforts to strengthen the tooth-resin interface have identified chemical agents with dentin collagen cross-linking potential and antimicrobial activities. The purpose of the present study was to assess protective effects of bioactive primer against secondary caries development around enamel and dentin margins of class V restorations, using an in vitro bacterial caries model. Class V composite restorations were prepared on 60 bovine teeth (n=15) with pretreatment of the cavity walls with control buffer solution, an enriched fraction of grape seed extract (e-GSE), 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide, or chlorhexidine digluconate. After incubating specimens in a bacterial model with Streptococcus mutans for four days, dentin and enamel were assessed by fluorescence microscopy. Results revealed that only the naturally occurring product, e-GSE, significantly inhibited the development of secondary caries immediately adjacent to the dentin-resin interface, as indicated by the caries inhibition zone. No inhibitory effects were observed in enamel margins. The results suggest that the incorporation of e-GSE into components of the adhesive system may inhibit secondary caries and potentially contribute to the protection of highly vulnerable dentin-resin margins.

Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial.

The incidence of insulin resistance and metabolic syndrome correlates with the availability of magnesium (Mg). We studied the effect of oral Mg supplementation on insulin sensitivity and other characteristics of the metabolic syndrome in normomagnesemic, overweight, insulin resistant, non-diabetic subjects. Subjects were tested for eligibility using oral glucose tolerance test (OGTT) and subsequently randomized to receive either Mg-aspartate-hydrochloride (n = 27) or placebo (n = 25) for 6 months. As trial endpoints, several indices of insulin sensitivity, plasma glucose, serum insulin, blood pressure and lipid profile were determined. Mg supplementation resulted in a significant improvement of fasting plasma glucose and some insulin sensitivity indices (ISIs) compared to placebo. Blood pressure and lipid profile did not show significant changes. The results provide significant evidence that oral Mg supplementation improves insulin sensitivity even in normomagnesemic, overweight, non-diabetic subjects emphasizing the need for an early optimization of Mg status to prevent insulin resistance and subsequently type 2 diabetes.

Script-driven imagery of self-injurious behavior in patients with borderline personality disorder: a pilot FMRI study.

OBJECTIVE: Self-injurious behavior (SIB) is one of the most distinctive features of borderline personality disorder (BPD) and related to impulsivity and emotional dysregulation. METHOD: Female patients with BPD (n = 11) and healthy controls (n = 10) underwent functional magnetic resonance imaging while listening to a standardized script describing an act of self-injury. Experimental sections of the script were contrasted to the neutral baseline section and group-specific brain activities were compared. RESULTS: While imagining the reactions to a situation triggering SIB, patients with BPD showed significantly less activation in the orbitofrontal cortex compared with controls. Furthermore, only patients with BPD showed increased activity in the dorsolateral prefrontal cortex during this section and a decrease in the mid-cingulate while imagining the self-injurious act itself. CONCLUSION: This pattern of activation preliminary suggests an association with diminished emotion regulation, impulse control as well as with response selection and reappraisal during the imagination of SIB.

Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjögren's syndrome.

BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjögren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

Immunonutrition--supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients.

BACKGROUND: Immunonutrition with omega-3 fatty acids and the "conditionally essential" amino acids arginine, glutamine, cysteine, and taurine can enhance the immune response in critically ill patients. This is due to the immunomodulating properties of these nutrients. Immunonutrition is especially important when a patient's immune response is compromised, as is the case post-operatively or after trauma. Immune deficiency is severely aggravated in sepsis and the systemic inflammatory response syndrome (SIRS). The resulting metabolic stress is characterized by glycolysis, lipolysis, and proteolysis, which may escalate to an hypercatabolic response or "autocannabilism." Catabolic metabolism results in insufficiency of both specific and unspecific immunocompetent cells. CONCLUSIONS: Immunonutrition should be started early in such patients for an optimal beneficial effect, preferably via the enteral route. It should include medium chain and long chain triglycerides, polyunsaturated omega-3 and omega-6 fatty acids (in the ratio 1:2), olive oil, and conventional amino acid preparations supplemented with the conditionally essential amino acids arginine, glutamine, cysteine, and taurine.

Supplementation with vitamin C, vitamin E or beta-carotene influences osmotic fragility and oxidative damage of erythrocytes of zinc-deficient rats.

Dietary zinc deficiency in rats causes increased osmotic fragility of their erythrocytes. In this study, the influence of supplementary antioxidants (vitamin C, vitamin E or beta-carotene) on osmotic fragility, oxidative damage and components of the primary defense system of erythrocytes of zinc-deficient rats was investigated. Indicators of hemolysis in vivo were also examined. Five groups of 12 male rats were force-fed a zinc-adequate diet (control rats), a zinc-deficient diet or a zinc-deficient diet enriched with vitamin C, vitamin E or beta-carotene. Compared with the control rats, the rats fed the zinc-deficient diet without supplementary antioxidants had greater red blood cell osmotic fragility, higher concentrations of thiobarbituric acid-reactive substances and alanine, higher glutathione S-transferase activity, lower concentration of glutathione and activity of glutathione peroxidase as well as lower activity of superoxide dismutase in plasma (P < 0.05). Supplementation with antioxidants generally improved osmotic fragility in zinc-deficient rats without influencing zinc concentration or alkaline phosphatase activity in plasma, indicators of zinc status. At some of the hypotonic saline concentrations tested, vitamin C and beta-carotene significantly affected osmotic fragility. The zinc-deficient rats fed a diet without supplementary antioxidants had significantly higher concentrations of alanine in erythrocytes than the zinc-deficient rats supplemented with vitamin C, vitamin E or beta-carotene and had significantly higher levels of thiobarbituric acid-reactive substances in erythrocytes than the rats supplemented with beta-carotene. There was no indication of hemolysis in vivo in rats fed zinc-deficient diets. The results show that supplementary antioxidants decrease osmotic fragility and oxidative damage of erythrocytes in zinc-deficient rats.

Influence of vitamin C, vitamin E and beta-carotene on the osmotic fragility and the primary antioxidant system of erythrocytes in zinc-deficient rats.

The present study was designed to investigate the effect of antioxidant supplementation on the in vitro osmotic fragility of erythrocytes from zinc-deficient rats. Rats were fed either a zinc-adequate diet, zinc-deficient diet or a zinc-deficient diet enriched either with vitamin C or vitamin E or beta-carotene. Components of the primary antioxidant system of erythrocytes, parameters of hemolysis in vivo and indicators of liver injuries were also examined. In order to ensure adequate and identical food intake rats were force-fed by intragastric tube. The supplementation with antioxidants led to a marked improvement of the osmotic fragility without having influenced zinc status of the animals and components of the antioxidant system. The strongest effect was exerted by vitamin E. The rats fed the zinc-adequate diet (control group) showed unusually high values of erythrocytes osmotic fragility. Therefore there was no difference between control group and zinc-deficient group. A possible reason for this is discussed. Zinc deficiency led to a reduction of serum zinc concentration and alkaline phosphatase activity as well as to changes in the antioxidant system of erythrocytes characterized by a decrease of glutathione and an increase of glutathione S-transferase activity. Superoxide dismutase activity in serum decreased. There was no indication for hemolysis in vivo and for liver injuries.

Comparative efficacy of sunscreen reapplication regimens in children exposed to ambient sunlight.

Undercompliance with sunscreen reapplication recommendations is a probable factor in suboptimal childhood ultraviolet radiation (UVR) protection. However, improving on the ability of sunscreens to absorb UVR without requiring frequent reapplication is difficult because the models most frequently used to develop and evaluate photoprotectants have only a limited ability to incorporate behavioral and environmental variables that are primarily responsible for loss of sunscreen efficacy. Hence, the objective of the present work was to develop a method to evaluate the efficacy of various regimens of sunscreen reapplication in children, under conditions of unrestricted behavior and exposure to ambient sunlight. Ninety-eight children, ages 7-12, Fitzpatrick skin types I-III, were divided between two study groups. The majority were types I-II, and all types were approximately equally represented between the groups. The children received single or multiple applications of a sun protection factor 25 sunscreen to preassigned lateral halves of the body and engaged in unrestricted activities throughout a 6- (group I) or 8-h (group II) period of sun exposure at a seaside location. The end measurement for these studies was incidence and severity of erythema 18 to 22 h after peak UV exposure. The results obtained showed that 1 or 4 sunscreen applications yielded comparable erythema protection after a 6-hour sun exposure, totaling 13 minimal erythema doses (MED). However, after an 8-h, 21 MED exposure, incidence and severity of erythema was greater at body sites treated with 1 compared with 5 sunscreen applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Tyrosine and N-carbamoyl-tyrosine in end-stage renal disease during continuous ambulatory peritoneal dialysis.

Lower-than-normal tyrosine concentrations of unexplained pathogenesis in plasma and intracellular body water have been reported in patients with chronic renal failure. We found a derivative of tyrosine that is not measured by the usual methods of amino-acid analysis because its alpha-amino group is blocked and cannot react to form other derivatives. An in vivo covalent reaction with urea-derived cyanate forms alpha-amino-carbamoyl-tyrosine (N-C-Tyr) in patients with end-stage renal disease. A longitudinal study of patients with end-stage renal disease who were treated with continuous ambulatory peritoneal dialysis shows that plasma that is obtained within 4 hours of the morning meal contains 70.1 +/- 6 mumol/L of tyrosine (mean +/- SEM) and 77.2 +/- 12 mumol/L of N-C-Tyr (mean +/- SEM). Thus there is a molecule of N-C-Tyr for each molecule of tyrosine present. The carbamoylation index or ratio of N-C-Tyr to tyrosine, blood urea nitrogen, episodes of peritonitis, and changes in dialysis protocol were compared. A reduction in the number of peritoneal dialysis exchanges resulted in parallel increases in carbamoylation index and blood urea nitrogen. Altering dialysis by increasing the number of exchanges or adding supplemental hemodialysis resulted in a decrease in the carbamoylation index with a delayed decrease in blood urea nitrogen. We found a significant increase of N-C-Tyr (p = 0.005) and of the carbamoylation index (p = 0.004) during six episodes of peritonitis compared with 10 periods of no peritonitis in two patients who had multiple episodes of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Salmonella arizona arthritis and septicemia associated with rattlesnake ingestion by patients with connective tissue diseases. A dangerous complication of folk medicine.

Snakes constitute the main reservoir of Salmonella arizona, which are opportunistic pathogens in patients with serious underlying diseases. The 2 may meet when such patients ingest uncooked snake flesh, most often as a folk remedy for arthritis or other conditions. We have seen 11 patients in whom Salmonella arizona infection was documented. Six had systemic lupus erythematosus and another had dermatomyositis and are described in detail. All 7 had received prednisone, which was combined with azathioprine in 3. Five developed septic arthritis, including the site of a hip prosthesis in one patient. A history of dessicated rattlesnake ingestion as a "natural" remedy in either capsule or powder form was obtained in all but one of the 7 patients. Patients often think that if natural or folk remedies are not helpful they also are not harmful and, therefore, safe and worth trying. We disprove that belief and call attention to the perils of one such remedy: dessicated rattlesnake, particularly when ingested by patients with connective tissue diseases who may be immunocompromised.

In vivo release by histamine agonists and antagonists of endogenous catecholamines in the cat hypothalamus.

The posterior hypothalamus of anaesthetized cats was superfused through a push-pull cannula with histamine agonists and antagonists and the release of endogenous catecholamines was determined in the superfusate. Hypothalamic superfusion with histamine, 2-methylhistamine (H1-agonist), dimaprit (H2-agonist) or metiamide (H2-antagonist) enhanced the release of the catecholamines dopamine, noradrenaline and adrenaline. The releasing effects of these substances depended on the presence of calcium ions. Superfusion with 2-pyridylethylamine (H1-agonist) was virtually ineffective, while superfusion with 2-thiazolethylamine (H1-agonist) enhanced the rates of release of noradrenaline and adrenaline without influencing the release of dopamine. Superfusion with mepyramine (H1-antagonist) inhibited the release of noradrenaline and adrenaline without affecting the release of dopamine. Hypothalamic superfusion with a concentration of procaine which was equi-anaesthetic to that of mepyramine was ineffective. Ranitidine (H2-antagonist) did not alter the rates of release of the catecholamines. The releasing effect of histamine was inhibited on hypothalamic superfusion with mepyramine and ranitidine. Ranitidine also inhibited the releasing effects of dimaprit and 2-methylhistamine thus indicating that the releasing action of the latter compound was mainly due to stimulation of H2-receptors. These data suggest that blockade of H1-receptors of the posterior hypothalamus reduces the release of noradrenaline and adrenaline, while stimulation of H1-receptors seems to increase the rates of release of these two catecholamines. Stimulation of H2-receptors enhances the release of all three catecholamines. Thus, dopaminergic neurones of the hypothalamus seem to possess H2-receptors, while noradrenergic and adrenergic neurones possess H1- and H2-receptors.

Effect of the calcium channel blocker nifedipine on Raynaud's phenomenon. A controlled double blind trial.

Eighteen patients with Raynaud's phenomenon (RP) of various etiologies completed a 10-week double blind parallel trial of the calcium channel blocker nifedipine (n = 10) versus placebo (n = 8). Patients on nifedipine were found to have had significant reduction of the number of episodes of RP but there were no differences in the intensity of episodes in patients taking nifedipine between the 1st and 6th visits nor between the nifedipine and placebo patient groups. Nifedipine seems to be helpful in the management of RP and was effective for the duration of this study.

Effects of short-lasting and long-lasting blood pressure changes on the release of endogenous catecholamines in the hypothalamus of the conscious, freely moving rabbit.

In anaesthetized rabbits guide cannulae were stereotaxically inserted into the anterior hypothalamic area and into the posterior hypothalamic nucleus. Additionally, catheters were inserted into the carotid artery and the jugular vein. Some days after the operation push-pull cannulae were inserted through the guide cannulae into the hypothalamic regions of the conscious, freely moving animal. The areas were superfused with artificial CSF and the release of the endogenous catecholamines dopamine, noradrenaline and adrenaline was determined in the superfusates. In the two hypothalamic regions the resting release of the catecholamines rhythmically varied with time at approximately 70 min cycles. A rise in blood pressure induced by the intravenous injection of noradrenaline or tramazoline enhanced the rates of release of the catecholamines in the anterior hypothalamic area. A fall of blood pressure elicited by the intravenous injection of nitroprusside or chlorisondamine decreased the release of the catecholamines in this hypothalamic area. The changes in blood pressure coincided with the changes in the rates of release of the catecholamines in the anterior hypothalamic area. These and previous results concerning changes in the release of endogenous catecholamines in the posterior hypothalamic nucleus also indicate that in the conscious, freely moving rabbit changes in blood pressure lead to counteracting alterations in the release of catecholamines in the two hypothalamic regions.

[Vaginal closure using the purse string suture method in elderly women with total prolapse]. / Scheidenverschluss durch Schnürnaht bei alten Frauen mit Totalprolaps.

The occlusion of the vagina by a shirodkar type string suture is an emergency procedure. As a temporary measure in old patients with procedentia this procedure relieves the symptoms of the prolapse during the time needed to prepare the patient for surgery or the time needed by the patient to decide to have the operation performed. For severely ill in-operable patients the purse string occlusion of the vagina is a simple method to eliminate the discomfort of the procedentia. The procedure can be done under local anaesthesia and can be repeated.

The release of endogenous catecholamines in the cat hypothalamus is affected by spinal transection and drugs which change the arterial blood pressure.

1. In anesthetized cats, posterior and anterior hypothalamic areas were superfused with CSF through double-walled cannulae. The release of endogenous catecholamines (dopamine, noradrenaline and adrenaline) was determined in the superfusate by a radioenzymatic assay. 2. Transection of the brain caudal to the hypothalamus almost abolished the release of catecholamines in the posterior hypothalamic area, while that in the anterior hypothalamic area was moderately decreased. A circular transection around the hypothalamus greatly reduced the release of catecholamines in the anterior hypothalamic area. It is concluded that the catecholaminergic nerve endings of the anterior hypothalamic area do not originate entirely from cell bodies located in the brain stem. 3. Spinal transection elicited a pressor response which was followed by a fall of the arterial blood pressure. The pressor response was associated with increased rates of release of the catecholamines in the anterior hypothalamic area, while the release of catecholamines in the posterior hypothalamic area was reduced. The fall of blood pressure enhanced the rates of release of the catecholamines in the posterior hypothalamic area and reduced their release in the anterior hypothalamic area. 4. Chlorisondamine i.v. caused a fall of blood pressure which was associated with an increased release of catecholamines in the posterior hypothalamic area and a decrease in the rates of release in the anterior hypothalamic area whilst i.v. tramazoline elicited a pressor response and enhanced the rates of release of the catecholamines in the anterior hypothalamic area. 5. It is concluded that pronounced changes in the arterial blood pressure affect the release of catecholamine in opposite direction in the two hypothalamic areas to counteract the blood pressure change.