Pyridostigmine Bromide (PYR) Alters Immune Function in B6C3F1 Mice

Pyridostigmine bromide (PYR) is an anticholinesterase drug indicated for the treatment of myasthenia gravis and neuromuscular blockade reversal. It acts as a reversible cholinesterase inhibitor and was used as a pretreatment for soldiers during Operation Desert Storm to protect against possible nerve gas attacks. Since that time, PYR has been implicated as a possible causative agent contributing to Gulf War Illness. PYR's mechanism of action has been well-delineated with regards to its effects on the nervous system, yet little is known regarding potential effects on immunological function. To evaluate the effects of PYR on immunological function, adult female B6C3F1 mice were gavaged daily for 14 days with PYR (0, 1, 5, 10, or 20 mg/kg/day). Immune parameters assessed were lymphoproliferation, natural killer cell activity, the SRBC-specific antibody plaque-forming cell (PFC) response, thymus and spleen weight and cellularity, and thymic and splenic CD4/CD8 lymphocyte subpopulations. Exposure to PYR did not alter splenic and thymus weight or splenic cellularity. However, 20 mg PYR/kg/day decreased thymic cellularity with decreases in both CD4 + /CD8 + (20 mg/kg/day) and CD4 - /CD8 - (10 and 20 mg/kg/day) cell types. Functional immune assays indicated that lymphocyte proliferative responses and natural killer cell activity were normal; whereas exposure to PYR significantly decreased primary IgM antibody responses to a T-cell dependent antigen at the 1, 5, 10 and 20 mg/kg treatment levels for 14 days. This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses.     

Catecholamine metabolism in humans exposed to pesticides

Plasma levels of epinephrine (E) and norepinephrine (NE) and 24-hour urinary excretion rates of E, NE, total metanephrines (M), and 3-methoxy-4-hydroxy-mandelic acid (VMA) were compared in 20 control subjects and in 23 persons exposed intensively to a mixture of DDT, parathion, and carbaryl. All subjects were male; 22 were white and 21 nonwhite. In the exposed group, total plasma DDT was 38.9 ppb and red cell cholinesterase was 11.99 μm/min/ml as compared, respectively, with 6.7 ppb (P < 0.005) and 13.65 μm/min/ml (P < 0.05) in the controls. Plasma levels and excretion rates of E were significantly lower in exposed than in control subjects. Excretion rates of NE, M, and VMA, as well as plasma levels of NE, were similar in the two groups. Systolic blood pressure correlated significantly with total plasma DDT (R = 0.55). Systolic and diastolic pressures were negatively correlated with red cell cholinesterase (R = ?0.39). These results in humans are not consistent with previously published data in animals, possibly due to species differences, but more likely due to difference in dosage between the animal studies and human exposure. It is suggested that future studies in animals include dose-response curves.     

Release of vasopressin by angiotensin II.

To test the hypothesis that angiotensin II releases antidiuretic hormone (ADH) after injection into ventricular cerebrospinal fluid, conscious adult male Sprague-Dawley rats with a lateral cerebroventricular cannula received an intraventricular injection of 0, 10, 50, or 100 ng angiotensin II. Trunk blood was collected 90 seconds later for radioimmunoassay of ADH. Plasma ADH, pg/ml (mean plus or minus S. E.), for the four dose levels were 2.8 plus or minus 0.7, 9.6 plus or minus 2.5, 22.6 plus or minus 5.6 and 25.0 plus or minus 5.0, respectively. The increases produced by angiotensin were statistically significant (p smaller than 0.05). Plasma ADH of the 10 ng group was intermediate between control and the two highest angiotensin doses (p smaller than 0.05), suggesting a dose-response relationship. These data provide direct evidence that angiotensin releases ADH by central mechanisms.     

Circumscribed osteoatrophy of the skull--a late symptom in bruxism

We present a case showing circumscribed osteoatrophy of the tabula externa and diploe of the skull following bruxism as a late symptom, which was induced by marked hypertrophy of the temporal muscle going with myogenic lockjaw.     

Characterization of haemorrhages at the origin of the sternocleidomastoid muscles in hanging

Haemorrhages at the periostal-clavicular origin of the sternocleidomastoid muscles were found in 52 out of 54 cases of death by hanging. This cervical haemorrhage is most frequently found in death by hanging, but only seldomly seen in other causes of death and can therefore be regarded as being typical for death by hanging. The frequency of this finding on the side of the highest point of the ligature mark is significantly higher, thereby supporting the hypothesis of extension as the causative mechanism. External cardiac massage and assisted breathing have no influence on the occurrence of haemorrhages. Histology shows the haemorrhages to be mainly directly epiperiostal, however, many cases displayed concurrent sub- and intraperiostal extravasations. Artificial post mortem production of these findings is discussed in the light of the literature.     

Recent data on the structure and function of collagenases

Four research projects on bacterial and vertebrate collagenases and their therapeutical application are discussed: induction of the production of a bacterial collagenase, proteolytic specificity of the two types of collagenases, their structure-function relations, and the application of the bacterial collagenase in the treatment of burns and ulcers.     

Murray Valley encephalitis acquired in Western Australia.

OBJECTIVE: To report a recent fatal case of encephalitis associated with evidence of Murray Valley encephalitis virus infection, only the second fatality from this infection in Western Australia. CLINICAL FEATURES: An 18-month-old Aboriginal boy was admitted to hospital in northwest Western Australia with proven Haemophilus influenzae type b meningitis. INTERVENTION AND OUTCOME: After an initial good response to antibiotics (amoxycillin and cefotaxime) he relapsed and died with evidence of encephalitis. Analysis of serum showed a high titre of antibody to Murray Valley encephalitis (MVE) virus with the presence of specific IgM. No evidence was found for other infective agents. CONCLUSION: It is likely that this child died from MVE which followed his bacterial meningitis. Of the strains of mosquitoes trapped in the area of suspected infection 77.8% were Culex annulirostris, the major vector species for MVE. No MVE virus was isolated from these mosquitoes, but serum from one of the sentinel chickens contained MVE virus antibodies, indicating the presence of the virus in that region.     

D20S19, linked to low voltage EEG, benign neonatal convulsions, and Fanconi anaemia, maps to a region of enhanced recombination and is localized between CpG islands.

Recent linkage studies located genes responsible for the low voltage EEG, benign neonatal convulsions and for the Fanconi anaemia to the vicinity of the VNTR marker CMM6 (D20S19). Physical mapping experiments using pulsefield electrophoresis in the distal part of chromosome 20q were chosen as a first step towards cloning of these genes. The observed pattern of shared fragments lead to the locus order 'tel-IP20K09-RMR6-CMM6-MS214-cen', which differs from previously reported genetic linkage maps. The physical intervals between these probes are markedly shorter compared with the genetic distances. Clusters of rare cutter sites around CMM6 point to at least four closely related CpG islands.