Coxsackievirus-positive cervices in women with febrile illnesses during the third trimester in pregnancy

Coxsackievirus B5 infection was demonstrated in five of seven third-trimester pregnant women with undifferentiated febrile illnesses or aseptic meningitis. Coxsackievirus B5 was recovered from the cervix and throat in four women and from the rectum in three. No obvious illnesses were evident in the babies. These findings suggest that previously unrecognized cervical enterovirus carriage or infection is common in infected pregnant women in the last trimester and that subsequent neonatal infection at delivery may result.     

Signet-ring cell carcinoma of the urinary bladder primary presentation as a Krukenberg tumor

A 34-year-old female presented with a right ovarian Krukenberg tumor, which initially was thought to be a granulosa cell tumor. Eight months later, necropsy revealed a primary signet-ring cell carcinoma (SRCC) of the urinary bladder. When occurring in females, this rare bladder tumor often exhibits ovarian metastases. This case appears to be the first reported example of a signet-ring cell carcinoma of the bladder presenting as a Krukenberg tumor.     

In vivo 31P NMR studies of the hepatic response to L-ethionine in anesthetized rats

Phosphorus-31 surface coil spectroscopy has been used to study the effects of L-ethionine administration on the hepatic metabolism of the anesthetized Sprague-Dawley rat. ATP levels were found to decrease by approximately 30% 3 to 4 hr after administration of 1 mg/g body wt of L-ethionine to the anesthetized rat by gastric gavage. ATP levels returned to control values approximately 8 hr postadministration. The relatively small decrease in ATP level was confirmed by extraction and conventional enzyme assay and is a consequence of the mode of administration of the ethionine. Hepatic inorganic phosphate levels rose concomitantly with the ATP fall. There were no significant changes in either cellular pH or Mg2+ levels as monitored by the 31P shifts of sensitive metabolites. In vivo 31P NMR spectroscopy provides a promising approach to study the effects of hepatotoxicants on cellular ATP, pH, and Mg levels.     

Developmental toxicity of halogenated acetonitriles: drinking water by-products of chlorine disinfection

The developmental toxicity of acetonitrile and 5 halogenated derivatives was examined with an in vivo teratology screen adapted for use in the Long-Evans rat. The screen was extended to an evaluation of growth till postnatal Days 41-42, and weight of several organs at sacrifice. Acetonitrile was without developmental effects even at doses toxic to the dam. Of the halogenated compounds, treatment with trichloroacetonitrile (TCAN) and dichloroacetonitrile (DCAN) resulted in reduced fertility and increased early implantation failure. There was no effect on litter size in females bearing live litters, but pup birth weight was reduced in all litters exposed to halogenated compounds. Perinatal survival of the pups was adversely impacted by DCAN and TCAN. Postnatal growth till Day 4 was reduced by DCAN and bromochloroacetonitrile (BCAN) while growth till Day 42 was consistently affected only by TCAN. Some general observations were made on the usefulness of the criteria used in the screen, and TCAN, the most toxic of the halogenated compounds, was selected for further in-depth evaluation.     

Effect of mosapride on Kv4.3 potassium channels expressed in CHO cells

Mosapride and cisapride are gastroprokinetic agents with 5-hydroxytryptamine₄ receptor agonist activity and have been widely used in the treatment of a variety of gastrointestinal disorders. The effects of mosapride and cisapride on cloned Kv4.3 channels stably expressed in Chinese hamster ovary cells were investigated using the whole-cell patch-clamp technique. Mosapride and cisapride inhibited Kv4.3 in a concentration-dependent manner with IC₅₀ values of 15.2 and 9.8 μM, respectively. Mosapride accelerated the rate of inactivation and activation of Kv4.3 in a concentration-dependent manner and thereby decreased the time to peak. The rate constants of association (k ₊₁) and dissociation (k _?1) for mosapride were 9.9 μM^?1 s^?1 and 151.3 s^?1, respectively. The K _D (k _?1/k ₊₁) was 16.2 μM, similar to the IC₅₀ value calculated from the concentration–response curve. Voltage-dependent inhibition by mosapride was observed in the voltage range for channel opening but was not observed over a voltage range in which all Kv4.3 channels were open. Both the steady-state activation and inactivation curves of Kv4.3 were shifted in the hyperpolarizing direction in the presence of mosapride. Mosapride also caused a substantial acceleration in closed-state inactivation of Kv4.3. Mosapride produced use-dependent inhibition, which was consistent with a slow recovery from inactivation of Kv4.3. M1 and norcisapride, the major metabolites of mosapride and cisapride, respectively, had little or no effect on Kv4.3. These results indicate that mosapride inhibits Kv4.3 by both preferential binding to the open state of the channels during depolarization and acceleration of the closed-state inactivation at subthreshold potentials.     

An evaluation of chemical photoreactivity and the relationship to phototoxicity

The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290–700 nm, and that are either applied locally/topically, or “reach” (EMEA)/“significantly partition” (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and a fivefold cross-validation PLS algorithm were used to evaluate the relationship between subsets of photophysical and photochemical parameters with the 3T3 NRU PIF/MPE (Photo Irritation Factor/Mean Photo Effect) results. The parameters most indicative of a 3T3 NRU positive PIF or MPE score were the extent of degradation in solution, the quantum yield of formation of singlet oxygen and the relative formation of superoxide anion. The results demonstrate that while absorption of light is critical to the induction of a light-induced process, it is the resultant events that may be used to predict the 3T3 NRU assay result. It is therefore proposed that the trigger for photosafety testing be revised to include a molecular basis for photoreactivity. From this limited investigation, estimated thresholds leading to 3T3 NRU positive results due to photodegradation, formation of singlet oxygen quantum yield or a relative superoxide anion formation value are proposed.     

Some poststimulatory effects on the whole nerve action potential

Short-term poststimulatory effects on the N1 component of the auditory-nerve compound action potential (CAP) were investigated in Mongolian gerbils. Some effects of conditioner level, conditioner frequency and probe level were assessed. In most cases, poststimulatory decrements occurred. The decrements were independent of probe intensity when the conditioner was close in frequency and of equal or less intensity than the probe. At some other conditioner frequencies, decrements decreased as probe intensity increased. Departures from these relationships occurred when a more intense conditioner was applied. In some instances, increases in CAP amplitude were also observed. The roles of single unit responses including spread of cochlear excitation, and possible mechanisms for poststimulatory facilitation are discussed.     

Levocabastine. Evaluation in the histamine and compound 48/80 models of ocular allergy in humans

The efficacy of a new antihistamine, levocabastine, in alleviating the ocular allergic reactions induced by both histamine and 48/80 was evaluated in humans. Levocabastine (0.5%) was instilled in one eye of 30 volunteers, and vehicle in the contralateral eye. After 15 minutes, half of the subjects received histamine (25 mg/ml) and half, 48/80 (7.5 mg/ml). The signs and symptoms of allergy were graded clinically after 30 minutes. Compared with a buffer control, levocabastine significantly alleviated itching (P = 0.01), redness (P = 0.0156), and chemosis (P = 0.005) induced by histamine, and itching (P = 0.032) and redness (P = 0.029) induced by 48/80. The results from these pharmacologic models support the clinical use of levocabastine for the treatment of allergic conjunctivitis.     

The nasal junction scotoma in giant aneurysms

Thirteen giant aneurysms in ten patients were retrospectively reviewed. Careful visual field testing of both peripheral and central fields revealed an ipsilateral nasal scotoma in 7 of the 13 aneurysms (54%), or six of the ten patients. A review of 47 giant carotid aneurysms reported in the literature revealed 16 ipsilateral nasal scotomas (34%). The more common intraocular causes of ipsilateral nasal field defects were excluded by careful funduscopic examination. In the absence of intraocular pathologic characteristics, an ipsilateral nasal junction scotoma should alert the clinician to suspect the presence of an otherwise silent internal carotid artery aneurysm.