Changes of glycosaminoglycan composition of uterine myometrium of rabbit induced by female sex steroids

Glycosaminoglycan fractions were separately prepared from the myometrium of control, estrogen-treated, and estrogen-progesterone-treated rabbits after digestion with pronase. The glycosaminoglycan composition of each glycosaminoglycan fraction was determined by digestion with specific mucopolysaccharidases and nitrous acid. It was found that foregoing hormones showed no effects on the total glycosaminoglycan content, expressed as mg per g of the delipidated dry tissue. These hormones, however, markedly affected the glycosaminoglycan composition. As compared with the control, the estrogen-treatment decreased the contents of hyaluronic acid and dermatan sulfate, but increased those of chondroitin 4- and 6-sulfates. The effect of estrogen on the content of hyaluronic acid was strikingly enhanced by subsequent treatment with progesterone, and those of chondroitin 4- and 6-sulfates were also enhanced. On the other hand, progesterone abolished effect on the content of dermatan sulfate. Although no effect was observed on the content of heparan sulfate by the estrogen treatment, subsequent treatment with progesterone decreased the content of this glycosaminoglycan.     

Alcoholic hepatitis with and without alcoholic hyaline.

Sixteen cases of alcoholic hepatitis with alcoholic hyaline (Group I) and 13 cases without alcoholic hyaline (Group II) have been collected since 1970. These were most frequently found in the fifth decade in both groups. One female was found in Group I. Cases of about two-thirds of both groups were comsumers of 110 g or more of alcohol per day. No significant differences except fever and erythrocyte sedimentation rate were found in clinical and laboratory changes between both groups. Fatty change in liver biopsy specimens were more frequently seen in Group I than in Group II. The wedged hepatic venous pressure was markedly elevated in alcoholic hepatitis with cirrhosis and moderately elevated in alcoholic hepatitis without cirrhosis. Wedged hepatic venography showed the main portal trunk and extrahepatic collaterals, namely, reversal of the portal flow or such tendency in 2 out of 5 patients of Group I.     

Dramatic improvement in Down syndrome-associated cognitive impairment with donepezil

OBJECTIVE: To report 2 cases of patients with Down syndrome and severe cognitive impairment who gained dramatic improvements in quality of life (QOL) upon donepezil treatment. CASE SUMMARIES: Case 1. A 38-year-old woman with Down syndrome, diagnosed with secondary progressive dementia when her mental state had deteriorated rapidly after graduation from junior high school, started donepezil treatment. The loading dose was 3 mg/day and was increased to 5 mg/day for maintenance. One month after the dose was increased, adverse effects such as soft stool and urinary incontinence appeared. These adverse effects disappeared when the dose was decreased again to 3 mg/day. Her QOL improved dramatically with this minimal dose. She recovered verbal and written communication skills that she had lost for the past 21 years. Case 2. A 22-year-old man with Down syndrome, who had been diagnosed as having severe mental retardation, was put on donepezil therapy. Both loading and maintenance doses were 3 mg/day. His QOL had also dramatically improved, with some recovery in verbal communication. Transient agitation/violence and transient muscle weakness appeared during the first few months of treatment. DISCUSSION: Patients with Down syndrome may be more sensitive to donepezil therapy than others and may benefit from this medicine, although they may also have adverse effects more frequently. CONCLUSIONS: Donepezil may be a useful medicine for some patients with Down syndrome with severe cognitive impairment or mental retardation if the adverse effects are manageable.     

The effect of long term ethanol intake on the parotid gland in rats

To elucidate the effects of long term ethanol intake on the parotid gland, light and electron microscopic observations of the parotid glands from male Wistar rats that had been given 20% ethanol ad lib instead of water were carried out. The findings were compared with the changes in the pancreas previously reported (Kakizaki et al. 1987). The results were as follows: (1) Severe lesions involving lobular units of the parotid gland were found in three rats exposed to ethanol. (2) From the early stages of ethanol ingestion, the lateral interdigitations of acinar cells widened irregularly. In the striated ducts, basal enfoldings became also irregular and short, while the mitochondria (which were a slender rod shape and arranged parallel to the basal enfoldings in control rats) became swollen, developed a dark matrix, a decrease in the cristae, and showed random arrangement. (3) Later, both tortous proliferation of the intercalated ducts and destruction as well as irregular lamination of the basal lamina of the striated ducts were observed frequently. (4) The animals developing severe morphological changes in the pancreas following ethanol ingestion were different from the animals developing severe changes in the parotid gland.     

Acetylcholine-induced endothelium-dependent vascular smooth muscle relaxation in nitroglycerin-tolerant isolated rat aorta

Summary Nitroglycerin (NTG) tolerance is recognized clinically, and its pharmacological mechanism has been thought to be due to a decrease in the accumulation of cyclic GMP (cGMP) which is a second messenger of NTG. Endothelium-derived relaxing factor (EDRF) also relaxes vascular smooth muscle through the activation of soluble guanylate cyclase and the production of cGMP. The purpose of this study was to investigate acetylcholine (ACh)-induced endothelium-dependent relaxation and cGMP response in NTG-tolerant isolated rat aorta. Ring strips prepared from the thoracic aorta of male Wistar rats were mounted in tissue baths and contracted with 10^–6 M norepinephrine. NTG and ACh relaxation responses were compared before and after 1 h treatment with 5×10^–4 M NTG. The chronological changes in tissue cGMP levels by 10^–6 M NTG and ACh were compared between a control group (untreated) and NTG-tolerant group (treated with 5×10^–4 M NTG for 1 h). The NTG dose-response curve shifted markedly to the right, but the ACh dose-response curve shifted to the left after the induction of NTG tolerance. In the control group, both NTG and ACh elevated the tissue cGMP levels, but in the NTG-tolerant group only ACh elevated cGMP significantly. However, in the NTG-tolerant group, the cGMP increase induced by ACh was smaller than that in the control group.These results suggest that NTG tolerance does not decrease, but rather augments ACh-induced endothelium-dependent vascular smooth muscle relaxation in isolated rat aorta.     

CT scans essential after posttraumatic loss of consciousness

The frequency of "talk and deteriorate" in the emergency department (ED), subsequent deterioration of patients with seemingly "mild" head injury at the time of presentation, is summarized. Among the 1,073 patients with minor head injury treated in the last 5 years, five patients (0.5%) deteriorated in the ED. All of the five patients had experienced transient loss of consciousness (LOC) before presentation. Deterioration had occurred during treatment of trivial associated injuries in four-fifths of the cases. Computed tomography (CT) scans revealed four acute epidural hematomas and one cerebellar contusion. Retrospectively, immediate brain CT shortly after their arrival may have revealed the presence of traumatic intracranial hematomas before deterioration. Although routine use of CT scans in patients with mild head injury has been controversial, the authors conclude that CT scans should be taken if patients have experienced transient LOC to prevent or reduce the occurrence of deterioration in ED.     

Current status of diagnosis and treatment of invasive fungal infections in Japan: the influence of the new Japanese guidelines

One year after the release of the Japanese “Guidelines for the Diagnosis and Treatment of Deep-Seated Mycosis” we conducted a survey of clinicians to determine the extent to which the new guidelines had penetrated clinical practice, and compared these results with those of a previous survey. The responses to the current survey regarding the diagnosis and treatment had changed from those of the previous survey to reflect the new recommendations, showing that the guidelines have had an effect on clinical practice. However, the current survey highlights a need to provide more practical information in the guidelines for use in the clinical settings. In particular, physicians expect the guidelines to proactively provide more information about the features of both current and new drugs. In addition, an effective drug against the genus Aspergillus is eagerly awaited. However, because it is difficult to differentiate among filamentous fungi, there is a need for a drug with broad-spectrum coverage against filamentous fungi. Investigation of combination therapy consequently becomes necessary. Definitive diagnoses of invasive fungal infection are too scarce at the national level. The cooperation of clinicians for organizing more definitive diagnoses would be appreciated when the guidelines are revised.     

Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis

Endoplasmic reticulum (ER) stress response is important for protein maturation in the ER. Some murine models for bone diseases have provided significant insight into the possibility that pathogenesis of osteoporosis is related to ER stress response of osteoblasts. We examined a possible correlation between osteoporosis and ER stress response. Bone specimens from 8 osteoporosis patients and 8 disease-controls were used for immunohistochemical analysis. We found that ER molecular chaperones, such as BiP (immunoglobulin heavy-chain binding protein) and PDI (protein-disulfide isomerase) are down-regulated in osteoblasts from osteoporosis patients. Based on this result, we hypothesized that up-regulation of ER molecular chaperones in osteoblasts could restore decreased bone formation in osteoporosis. Therefore, we investigated whether treatment of murine model for osteoporosis with BIX (BiP inducer X), selective inducer BiP, could prevent bone loss. We found that oral administration of BIX effectively improves decline in bone formation through the activation of folding and secretion of bone matrix proteins. Considering these results together, BIX may be a potential therapeutic agent for the prevention of bone loss in osteoporosis patients.