Exacerbation of psychosis by misinterpretation of physical symptoms

Impaired processing of perceptual information is often a prominent aspect of psychotic disorders. Physical symptoms such as pain or discomfort may be either incorrectly perceived or misinterpreted by psychotic patients. Presented here is a series of cases in which somatic symptoms occurred in psychotic patients and worsened their psychotic states but only later were recognized as physical problems. Psychotic patients may be unable to comprehend or describe their physical symptoms adequately. Physical disorders of psychotic patients may be overlooked if clinicians are not vigilant and thorough in assessing the patients' complaints, especially if such complaints sound delusional or bizarre.     

Venous response to nitroglycerin is enhanced in young, healthy carriers of the 825T allele of the G protein beta3 subunit gene (GNB3)

OBJECTIVE: The ultimate mode of action by which nitroglycerin elicits vasodilation remains elusive. Animal studies point to an involvement of pertussis toxin-sensitive G proteins. The 825T allele of the GNB3 C825T polymorphism in the gene encoding the G protein beta3 subunit is associated with enhanced signal transduction via pertussis toxin-sensitive pathways in vitro. We hypothesized that G proteins have a role in nitroglycerin-mediated vasodilation and that carriers of the 825T allele would exhibit a stronger response to nitroglycerin. METHODS: We used the linear variable transducer technique to compare dorsal hand vein compliance in 28 young, healthy men with and without the T allele (n = 15 CC, n = 8 CT, and n = 5 TT). After individual dose-response curves to phenylephrine had been established, veins were preconstricted to 70% of the maximal phenylephrine-induced constriction. Nitroglycerin was then infused in ascending doses (0.02-2000 ng/min), and the vasodilatory response was measured. RESULTS: The vasodilatory response to nitroglycerin was significantly greater in carriers of the 825T allele. The maximal response to nitroglycerin was 102% +/- 6% venodilation in the CT/TT group and 78% +/- 5% in the CC control group (P =.0045) (mean difference, -24% +/- 8%; 95% confidence interval, 8%-40%). Comparison of the nitroglycerin dose-response curves by ANOVA confirmed an enhanced nitroglycerin-induced venodilation in 825T-allele carriers (P <.0001). CONCLUSION: Our results suggest that the GNB3 C825T polymorphism determines venous response to nitroglycerin and that G proteins may be involved in the signal transduction pathway.     

Effects of hypocaloric diet on sleep in young and old rats

Aging produces a loss in a number of behavioral and cognitive functions, including sleep. Hypocaloric diet is one of the few methods that have been shown to retard the effects due to age. However, the effects of such a diet on sleep have never been investigated. In the present study, 21 months old male F344 rats fed a 60% calorie-reduced diet continued to have a significant reduction in delta power (0.3-4 Hz EEG), less sleep following 12 h total sleep deprivation (TSD) and increased sensitivity to caffeine compared to young rats (3 months) fed a similar diet. These results indicate that caloric restriction is unable to prevent the decline in sleep that occurs with aging.     

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.     

Myosin-V colocalizes with MHC class II in blood mononuclear cells and is up-regulated by T-lymphocyte activation

Myosin-V is involved in organelle and vesicle trafficking in Saccharomyces cerevisiae and in other eukaryotic cells from yeast to human. In the present study, we determined by FACS that the major subpopulations of the peripheral blood mononuclear cells express myosin-V with similar fluorescence intensity. Confocal microscopy showed intense labeling for myosin-V at the centrosomal region and a punctate staining throughout the cytoplasm, frequently associated with the central microtubule arrays and the actin-rich cortex. Some degree of overlap with an endolysosomal marker and dynein light-chain 8 k was found at the cell center. Striking colocalization was observed with the major histocompatibility complex (MHC) class II molecules near the cell surface. Treatment with phytohemagglutinin, which induces T-lymphocyte activation, associated with MHC class II expression, increased the levels of myosin-V protein and mRNA for the three members of class V myosins. These data suggest that class V myosins might be involved in relevant functions in the immune response.     

High density lipoprotein-cholesterol changes in children with high cholesterol levels at birth

The predictive value of serum lipoprotein concentrations at birth for the same parameters later in life is under debate. A group of 20 children displaying high total cholesterol (TC) levels at birth (group 2) were compared at age 4 years with 18 control children who had presented a normal lipoprotein profile at birth (group 1). There was a significant correlation between TC, low density lipoprotein-cholesterol, high density lipoprotein (HDL)-cholesterol, and apolipoprotein (Apo) A-I levels at age 4 years and at birth. The increases in TC and HDL-cholesterol levels from birth to age 4 years were significantly lower (P < 0.05, P < 0.01, respectively) in group 2 than in the control group and inversely correlated with the concentrations of these parameters at birth. The increases in HDL-cholesterol and Apo A-I levels were higher in males while those of triacylglycerol and Apo B were higher in females (P < 0.05). However, the increases in TC and HDL-cholesterol were higher in controls (P< 0.05). Diets of children of both groups were similar regarding the energy contribution of saturated, monounsaturated and polyunsaturated fatty acids, although children from group 2 ate less fish and omega-3 fatty acids (P < 0.05). CONCLUSION: the present data suggest for the first time that when high density lipoprotein-cholesterol levels are high at birth, those levels increase less during the first four years of life. Moreover, low density lipoprotein-cholesterol increased about five times as much as high density lipoprotein-cholesterol did in controls and about 15 times as much as in the children with high cholesterol at birth.     

Benign paroxysmal positional vertigo in patients with Ménière's disease treated with intratympanic gentamycin

OBJECTIVES: To analyze the incidence and characteristics of benign paroxysmal positional vertigo (BPPV) in patients with Ménière's disease who did not respond to medical treatment and to whom intratympanic gentamycin treatment was proposed. STUDY DESIGN: This is a retrospective analysis of the patients in our database. A complete otoneurologic bedside examination of each patient, including assessment of positional nystagmus, was performed at the time of diagnosis and during the follow-up. RESULTS: Nine of 90 patients with Ménière's disease also had BPPV, which manifested in different ways. In 3 patients, BPPV preceded the onset of Ménière's symptomatology in the same ear; in 1, BPPV manifested after treatment for Meniere's disease had ended and the patient was in complete control of the spontaneous spells of vertigo; in 5 cases, recurrences of both Meniere's disease and the positioning symptomatology coincided. Treatment for each condition was conducted independently and favorable results were obtained after long-term follow-up when Meniere's disease and BPPV did not coincide simultaneously. In the group manifesting symptoms of both disorders at the same time, gentamycin treatment with the Canalith Repositioning Procedure and/or Semont maneuver partially resolved the symptoms. CONCLUSIONS: In the context of Ménière's disease, the sequence of appearance of BPPV relative to the spontaneous episodes must be taken into account when planning the treatment for each of the disorders, which should be considered independently. This pattern could also influence the prognosis for each disorder.     

Activity-dependent expression of simultaneous glutamatergic and GABAergic neurotransmission from the mossy fibers in vitro

GABAergic transmission in the mossy fiber (MF) projection of the hippocampus is not normally detected in the rat. However, seizures induce simultaneous glutamatergic and GABAergic transmission in this projection, which coincides with an overexpression of GAD(67) and vesicular GABA transporter (VGAT) mRNA in the dentate gyrus (DG) and MF. To test whether this plastic change could be induced in an activity-dependent fashion in the absence of seizures, I recorded intracellularly from slices/cells that served as their own control, before and after direct or synaptic kindling of the DG in vitro. As expected, synaptic responses of CA3 pyramidal cells to test pulse DG stimulation were blocked by perfusion of N-methyl-D-aspartate (NMDA) and non-NMDA receptors' antagonists. However, after kindling the perforant path (3 1-s trains of 0.1-ms pulses at 100 Hz, 1 min apart from each other every 15 min for 3 h), which potentiated synaptic responses without inducing epileptiform activity, the perfusion of glutamatergic antagonists blocked the excitatory synaptic potential and isolated a fast bicuculline-sensitive inhibitory synaptic potential. Immunohistochemical experiments confirmed the overexpression of GAD(67) in the kindled slices. If kindling stimulation was provided just for 1 h or if it was completed in the presence of the protein synthesis inhibitor, cycloheximide, the expression of the GABAergic potential was prevented. Alternatively, when control synaptic responses of a given cell were first blocked, the direct kindling stimulation over the same site during perfusion of glutamatergic antagonists resulted in the induction of fast GABAergic potentials after 16.6 +/- 0.9 kindling trials. Furthermore, a high spacial specificity of this phenomenon was evidenced by recording synaptic responses of a given pyramidal cell to two different MF inputs. After blockade of all synaptic responses with the perfusion of glutamatergic antagonists, one of the inputs was kindled, while synaptic responses between the kindling trials were monitored by applying test pulse stimulation to both inputs. After 17 +/- 1 trials, test pulse stimulation provided over the kindled site evoked GABAergic potentials, whereas test pulse stimulation delivered to the alternative nonkindled parallel MF input remained ineffective. The DG-evoked GABAergic responses were inhibited by the activation of GABA(B)R and mGluR, whereby activation of group III mGluR with L-2-amino-4-phosphonobutyric acid (L-AP4) was significantly more effective than the activation of group II mGluR with DCG-IV. These data demonstrate that GABAergic transmission from the MF projection has distinctive features in the adult rat, and that its induction is dependent on protein synthesis responding in an activity-dependent fashion.