Niemann-Pick type C disease associated with peripheral neuropathy

Niemann-Pick type C disease is an autosomal-recessive, inherited neurovisceral lipid storage disorder. This disease results from either protein NPC1 or HE1 deficiency, which leads to cholesterol metabolism disturbance and is characterized by early hepatosplenomegaly and progressive ataxia, dystonia, cataplexy, dysarthria, and dementia. We describe a 3 1/2-year-old patient with Niemann-Pick type C disease, who presented with regression in both cognitive and motor domains. Almost 10 months before admission to the hospital, the child developed progressive speech and behavioral changes, as well as gait disturbances with frequent falls. The examination demonstrated hepatosplenomegaly, ataxia, and vertical gaze palsy. Nerve conduction velocities demonstrated mild demyelinating peripheral neuropathy. Bone marrow examination revealed foam cells, and cholesterol esterification studies found massive accumulation of unesterified cholesterol and very low intracellular esterification of exogenous lipoprotein-derived cholesterol. These results indicate Niemann-Pick type C disease. Peripheral neuropathy is a rare complication in patients with Niemann-Pick type C disease, which certainly contributes to their neurologic deterioration.     

Immunologic evaluation of dental patient with history of hypersensitivity reaction to sodium hypochlorite

A 12-year-old girl, with a previous history of bronchial reaction and contact dermatitis to sodium hypochlorite, was referred for root canal treatment. Complete immunologic evaluation revealed a mild hypersensitivity condition, as it was assessed by the RAST investigation to different allergens and the DTH reactivity expressed though migration inhibition test. The absence of a serious immunologic disregulation in the patient's immunologic profile justified the term 'non-allergic hypersensitivity' to sodium hypochlorite to describe the condition.     

Effect of bacterial extracts on the immunologic profile in chronic relapsing brucellosis patients

Brucellosis is an intracellular bacterial disease of common incidence in Greece. Existing therapy is inadequate and a considerable proportion of patients become chronically ill and are immunocompromised. Defects of the monocyte-macrophage system and T-lymphocytes have been described in chronic brucellosis and can be restored after immunopotentiation therapy. Bacterial (Klebsiella pneumoniae) extracts exert immunostimulating effects on the monocyte-macrophage system and have already been used successfully in the prevention of common infections of the respiratory track. So we decided to investigate: 1) Leukocyte Migration Index (LMI), 2) Monocyte-macrophage random and directed migration against both nonspecific leukoattractant (casein) and disease specific antigens (Brucella melitensis, Brucella abortus), 3) Monocyte-macrophage phagocytosis index, 4) Delayed-type hypersensitivity (skin tests) against seven antigens, before (TO), during (T2), and after (T3) oral administration of bacterial (Klebsiella pneumoniae) extracts at conventional doses plus antibiotics or not. Our results show that: 1) Concerning the LMI, 4 out of 19 remained anergic at time T3 of the study, 2) Random migration was not affected during treatment, 3) Directed migration increased significantly without reaching control group values, 4) Phagocytosis index increased significantly and reached normal values at T3, 5) Delayed type hypersensitivity reactions (skin tests) increased significantly at the end of the study period. Reaction against Tuberculin and Candida antigens showed the most pronounced increase in skin reactivity. In conclusion, bacterial (Klebsiella pneumoniae) extracts improve peripheral monocyte locomotion and restore phagocytosis index, thus enhancing cellular immunity parameters in immunocompromised chronic brucellosis patients.     

Eosinophilic infiltration in the nasal mucosa of rhinitis patients: is it affected by the presence of asthma or the allergic status of the patients?

BACKGROUND: Asthma and rhinitis often coexist, and there is evidence to suggest that they have similar histopathologic features. OBJECTIVE: To examine whether the inflammatory infiltration in the nasal mucosa in rhinitis is affected by the presence of asthma and allergy. METHODS: Nasal mucosa biopsy samples were collected from 44 individuals: 18 with rhinitis and asthma (9 allergic and 9 nonallergic), 16 with rhinitis and no asthma (8 allergic and 8 nonallergic), and 10 nonallergic control subjects. The alkaline phosphatase-anti-alkaline phosphatase method was applied to 6-microm-thick cryostat sections using monoclonal antibodies against T cells (CD4 and CD8) and eosinophils (EG2). Slides were counted blindly, and results are expressed as cells per high-power field. RESULTS: Eosinophil counts were higher in the nasal mucosa of rhinitic patients vs controls. No differences in cellular infiltration were detected between rhinitic patients with and without asthma or between allergic and nonallergic patients. A trend toward higher CD4+ T-cell counts in the nasal mucosa of rhinitic patients was observed, whereas no differences were noted in CD8+ T-cell infiltration among the groups. CONCLUSION: Inflammatory infiltration, characterized by the presence of eosinophils and CD4+ T cells, was similar in the nasal mucosa in noninfectious rhinitis irrespective of the presence of asthma or the allergic status of the patient.     

The Effect of <Emphasis Type="SmallCaps">l</Emphasis>-arginine and Aprotinin on Intestinal Ischemia–reperfusion Injury

Background Intestinal ischemia/reperfusion (I/R) results in local mucosal injury, systemic injuries, and organ dysfunction. These injuries are characterized by altered microvascular and epithelial permeability and villous damage. Activation of neutrophils, platelets, and endothelial factors are known to be involved in this process. Cytokines such as TNF-α, IL-1, IL-6, and oxygen-derived free radicals are believed to be important pathogenic mediators. Capillary no-reflow is also known to play a role in I/R. The aim of our study was to examine the role of l-arginine, a known nitric oxide (NO) donor, and aprotinin, a protease inhibitor with multiple effects, on intestinal I/R. Methods Pigs weighing 20–25 kg were used. Ischemia was established by clamping the superior mesenteric artery (SMA) at its origin and was sustained for 2 hours. Duration of reperfusion was 2 hours. The animals were divided into four groups: group A, the control group, which was submitted to I/R injury only; group B, in which l-arginine was administered at a rate of 5 mg/kg/min during ischemia and continuing throughout reperfusion; group C, in which aprotinin was administered with an initial bolus dose of 20,000 U/kg during ischemia followed by a continuous dose at 50 U/hour throughout reperfusion; and group D in which both substances were administered. In all groups TNF-α, IL-1, and IL-6 levels were measured using ELISA at baseline, 2 hours of ischemia, and 1 hour and 2 hours of reperfusion. SMA blood flow was measured with a Doppler probe at baseline, 10 min, 1 hour, and 2 hours of reperfusion. Histological changes of the intestinal mucosa were examined and graded on a five-point scale in all groups. Results In the control group, levels of TNF-α, IL-1, and IL-6 were significantly increased during reperfusion (p < 0.05) compared to baseline. Administration of l-arginine and aprotinin led to suppression of the release of TNF-α, IL-1, and IL-6 during reperfusion in a statistically significant manner (all p < 0.05). A synergistic or additive effect of l-arginine and aprotinin was not observed. SMA blood flow in the control group was decreased (p > 0.05) during reperfusion compared to baseline. In animals treated with l-arginine and aprotinin, SMA blood flow during reperfusion was significantly increased (p < 0.05) compared to the control group. Histologic examination of the intestinal mucosa was characterized by flattening of the villi and necrosis in the control group. In the treated animals, less severe histological changes were noted. Conclusions Administration of l-arginine and aprotinin may lead to amelioration of intestinal I/R injury. We did not note a synergistic or additive effect of these two substances. These findings warrant further studies in clinical settings for future treatment efforts. This paper was presented as a poster at the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract, Los Angeles, California, May 20–24, 2006.     

Influence of menstrual cycle and oral contraceptives on tolerance to uncompensable heat stress

In this study we examined the influence of menstrual cycle phase and oral contraceptive use on thermoregulation and tolerance during uncompensable heat stress. Eighteen women (18–35 years), who differed only with respect to oral contraceptive use (n?=?9) or non-use (n?=?9), performed light intermittent exercise at 40°C and 30% relative humidity while wearing nuclear, biological and chemical protective clothing. Their responses were compared during the early follicular (EF, days 2–5) and mid-luteal (ML, days 19–22) phases of the menstrual cycle. Since oral contraceptives are presumed to inhibit ovulation, a quasi-early follicular (q-EF) and quasi-mid-luteal (q-ML) phase was assumed for the users. Estradiol and progesterone measurements verified that all subjects were tested during the desired phases of the menstrual cycle. Results demonstrated that rectal temperature (T _re) was elevated in ML compared with EF among the non-users at the beginning and throughout the heat-stress trial. For the users, T _re was higher in q-ML compared with q-EF at the beginning, and for 75?min of the heat-stress exposure. Tolerance times were significantly longer during EF [128.1 (13.4)?min, mean (SD)] compared with ML [107.4 (8.6)?min] for the non-users, indicating that these women are at a thermoregulatory advantage during the EF phase of their menstrual cycle. For the users, tolerance times were similar in both the q-EF [113.0 (5.8)?min] and q-ML [116.8 (11.2)?min] phases and did not differ from those of the non-users. It was concluded that oral contraceptive use had little or no influence on tolerance to uncompensable heat stress, whereas tolerance was increased during EF for non-users of oral contraceptives.     

Hypothermia augments non-cholinergic neuronal bronchoconstriction in pithed guinea-pigs.

Electrical stimulation at C4-C7 in the spinal canal of pithed guinea-pigs injected with atropine, d-tubocurarine and pentolinium caused frequency-dependent bronchoconstriction. Such non-cholinergic responses to electrical stimulation, unlike responses to substance P, were abolished by pretreatment with capsaicin but not by mepyramine or propranolol. Bronchoconstrictor responses to electrical stimulation were inversely related to rectal temperature (between 30-40 degrees C) whereas responses to substance P increased with increasing temperature over the same range. Ouabain (i.v.) augmented responses to electrical stimulation at 35-37 degrees C but depressed those at 30-32 degrees C. Both morphine and the alpha 2-adrenoceptor agonist B-HT920 (i.v.) inhibited non-cholinergic-mediated bronchoconstrictor responses at 30-32 degrees C. These results stress the importance of adequate control of body temperature in this preparation. Lowered body temperature may increase neuronal output of neuropeptides whilst depressing bronchial smooth muscle sensitivity. The data support previous conclusions regarding the role of Na+/K+ activated ATPase in temperature-induced changes in sensitivity to bronchoconstrictor stimuli.