Burning Mouth Syndrome

Burning mouth syndrome (BMS) is multifactorial in origin which is typically characterized by burning and painful sensation in an oral cavity demonstrating clinically normal mucosa. Although the cause of BMS is not known, a complex association of biological and psychological factors has been identified, suggesting the existence of a multifactorial etiology. As the symptom of oral burning is seen in various pathological conditions, it is essential for a clinician to be aware of how to differentiate between symptom of oral burning and BMS. An interdisciplinary and systematic approach is required for better patient management. The purpose of this study was to provide the practitioner with an understanding of the local, systemic, and psychosocial factors which may be responsible for oral burning associated with BMS, and review of treatment modalities, therefore providing a foundation for diagnosis and treatment of BMS.     

Autobiographical memory and suggestibility in children with autism spectrum disorder

Two paradigms were developed to examine autobiographical memory (ABM) and suggestibility in children with autism spectrum disorder (ASD). Children with ASD (N = 30) and typically developing chronological age-matched children (N = 38) ranging in age from 5 to 10 years were administered an ABM questionnaire. Children were asked about details of current and past personally experienced events. Children also participated in a staged event, and later were provided with true and false reminders about that event. Later, children again were interviewed about the staged event. The results from both paradigms revealed that children with ASD showed poorer ABM compared to controls. Generally, their ABM was marked by errors of omission rather than by errors of commission, and memory was particularly poor for early-life events. In addition, they were as suggestible as the typically developing children. The results are discussed in terms of applied and theoretical implications.     

Condom use prevents genital ulcers in women working as prostitutes. Influence of human immunodeficiency virus infection

Control of genital ulcer disease (GUD) is a proposed intervention to slow the dissemination of human immunodeficiency virus (HIV) infection. Programs for the control of sexually transmitted diseases (STD) should focus on groups of high-frequency transmitters, such as prostitutes and their clientele. This study illustrates the interaction between the prevalence of chancroid, use of barrier prophylaxis against STDs, and HIV infection in a population of female prostitutes in Nairobi. Four hundred and twenty three women were evaluated. Despite the increased use of condoms, the prevalence of genital ulcers remained constant between 1986-87 and 1987-88. Genital ulcer disease was simultaneously associated with HIV infection (adjusted odds ratio: 3.7, P less than .01) whereas it was independently and inversely associated with more consistent condom use (P less than .01). The authors conclude that genital ulcer disease can be controlled in these populations but concurrent HIV infection increases the difficulty of this intervention.     

Endothelial LSP1 is involved in endothelial dome formation, minimizing vascular permeability changes during neutrophil transmigration in vivo

The endothelium actively participates in neutrophil migration out of the vasculature via dynamic, cytoskeleton-dependent rearrangements leading to the formation of transmigratory cups in vitro, and to domes that completely surround the leukocyte in vivo. Leukocyte-specific protein 1 (LSP1), an F-actin-binding protein recently shown to be in the endothelium, is critical for effective transmigration, although the mechanism has remained elusive. Herein we show that endothelial LSP1 is expressed in the nucleus and cytosol of resting endothelial cells and associates with the cytoskeleton upon endothelial activation. Two-photon microscopy revealed that endothelial LSP1 was crucial for the formation of endothelial domes in vivo in response to neutrophil chemokine keratinocyte-derived chemokine (KC) as well as in response to endogenously produced chemokines stimulated by cytokines (tumor necrosis factor α [TNFα] or interleukin-1β [IL-1β]). Endothelial domes were significantly reduced in Lsp1(-/-) compared with wild-type (WT) mice. Lsp1(-/-) animals not only showed impaired neutrophil emigration after KC and TNFα stimulation, but also had disproportionate increases in vascular permeability. We demonstrate that endothelial LSP1 is recruited to the cytoskeleton in inflammation and plays an important role in forming endothelial domes thereby regulating neutrophil transendothelial migration. The permeability data may underscore the physiologic relevance of domes and the role for LSP1 in endothelial barrier integrity.     

TLR4 activation and IL-6-mediated cross talk between adipocytes and mononuclear cells synergistically stimulate MMP-1 expression

Obesity is associated with increased monocyte infiltration into adipose tissue and hence increased interaction between adipocytes and monocytes. Although it has been shown that matrix metalloproteinases (MMP) play a critical role in adipose tissue development, the effect of adipocyte and monocyte interaction on MMP production remains largely unknown. Furthermore, although it has been shown that Toll-like receptor 4 (TLR4), a receptor mediating innate immune response, plays an important role in the obesity-associated inflammation and insulin resistance, the effect of TLR4 activation in coculture of adipocytes and monocytes on MMP production has not been investigated. In this study, we cocultured adipocytes with U937 mononuclear cells in a Transwell coculture system and activated TLR4 with lipopolysaccharide or palmitic acid. We found that TLR4 activation and the coculture had a synergistic effect on MMP-1 production. In our further investigation on the underlying mechanisms, it was indicated that adipocyte-derived IL-6 and TLR4 activation acted in concert to synergistically stimulate MMP-1 expression by U937 cells. Taken together, this study has uncovered a novel mechanism potentially involved in MMP-1 up-regulation in adipose tissue, which may facilitate adipose tissue development and obesity.     

Peritoneal catheter implantation elicits IL-10-producing immune-suppressor macrophages through a MyD88-dependent pathway

Catheters are implanted into the peritoneal cavity during the process of peritoneal dialysis. Though these catheters may be effective and beneficial, the impact of catheters on the immune system is poorly understood. Catheters and other devices implanted in the peritoneal cavity elicit a foreign body reaction. However, the immunological consequences of this remain uncharacterized. To model this, catheters were implanted into the peritoneal cavity of healthy mice. Catheter implantation induced rapid cellular changes within the peritoneal cavity. Whereas B-cells and T-cells were reduced, catheter implantation was associated with the rapid expansion of F4/80-low-positive, CD11b-positive macrophages that elaborated IL-10, and suppressed T-cell division and Th1 skewing in co-culture assays. Peritoneal catheter elicited macrophages had increased Jmjd3 but reduced NF-κB activation, and their emergence was MyD88-dependent. Collectively, these studies indicate that foreign body implantation into the peritoneal cavity is associated with the expansion of suppressor macrophages. Whether peritoneal cavity catheter implantation may have systemic immunoregulatory roles remains to be explored.     

Different signaling mechanisms regulating IL-6 expression by LPS between gingival fibroblasts and mononuclear cells: seeking the common target

To reduce connective tissue IL-6 level stimulated by LPS, it is essential to control IL-6 expression in both mononuclear cells and fibroblasts. However, it is unclear whether the regulatory mechanisms for both cells are similar or not. In this study, we found that signaling pathways mediating LPS-stimulated IL-6 in mononuclear U937 cells and fibroblasts were different. Furthermore, our studies showed that while LPS activated AP-1 and NFκB in U937 cells, it only activated NFκB in fibroblasts. Analysis of nuclear AP-1 subunits showed that LPS stimulated c-Fos, Fra-1 and Jun D activities in U937 cells, but not fibroblasts. The lack of ERK involvement in LPS-stimulated IL-6 in fibroblasts was further supported by the observations that simvastatin, which is known to target ERK-AP-1, failed to inhibit LPS-stimulated IL-6 by fibroblasts. Finally, we showed that targeting NFκB pathway was highly effective in inhibition of LPS-stimulated IL-6 in coculture of U937 cells and fibroblasts.     

Role of p21 and cyclin E in normal and secalonic acid D-inhibited proliferation of human embryonic palatal mesenchymal cells

Secalonic acid D (SAD), a cleft palate-inducing teratogen, has been shown to inhibit proliferation/cell cycle progression in association with alteration in the levels of cell cycle regulators, p21 and cyclin E. These studies were conducted to test the hypotheses that p21 and cyclin E play an important functional role in normal human embryonic palatal mesenchymal (HEPM) cell cycle and that their up- and down-regulation, respectively, by SAD is functionally significant to its cell cycle block. Using small interfering RNA (siRNA) to silence p21 gene and transient transfection to overexpress cyclin E in control & SAD-treated HEPM cells, cell proliferation was assessed using a combination of cell numbers, thymidine uptake, CDK2 activity and Ki-67 expression. The results showed that silencing of p21 gene, although increased cell proliferation/numbers and CDK2 activity in normal HEPM cells, failed to counteract SAD-induced anti-proliferative effect despite inducing partial recovery of CDK2 activity. Similar effects were apparent with cyclin E overexpression. It is concluded that p21 and cyclin E are important for normal HEPM cell proliferation. However, SAD-induced deregulation of either protein, singly, may not be sufficient to induce anti-proliferative effect. Involvement of other cell cycle proteins such as cyclin D1 or of multiple proteins in SAD-induced cell cycle block needs to be examined.     

Detoxification of Nerium indicum roots based on Indian system of medicine: phytochemical and toxicity evaluations

Indian system of medicine describes the usage of certain very toxic plant based drugs after performing a detoxification process (Shodhana samskara). Nerium indicum is traditionally used as a medicine though known to cause severe allergic symptoms, tachycardia and gastrointestinal effects leading to fatalities. In this study, the detoxification (shodhana) for Nerium indicum was scientifically validated based on phytochemical and toxicity profiles. Shodhana was performed according to traditional literature. HPTLC densitometric studies were performed for the pre- and post-shodhana powders followed by sub-acute toxicity evaluation in rats. Preparative TLC and LC-MS showed the reduction of oleandrin peak in the post-shodhana sample. Prominent features of cardiotoxicity including tachycardia were noted in the pre-shodhana Nerium treated animals along with mortality. However, no such toxicity was encountered in the post-shodhana Nerium treated animals. Hence, using the recommended detoxification (shodhana), the toxicity of an important medicinal plant was significantly nullified. Such studies provide a scientific support towards our traditional medicinal practices using modem analytical and experimental methodologies and may prove to be very useful in establishing standard scientific procedures for routine and safe use of traditional medicines.