Molecular networking-guided investigation of the secondary metabolome of four Morus species and their in vivo neuroprotective potential for the mitigation of Alzheimer's disease.

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.

A multiplex metabolomic approach for quality control of Spirulina supplement and its allied microalgae (Amphora & Chlorella) assisted by chemometrics and molecular networking.

Microalgae species are of economic importance regarded as "green gold" being rich in bioactive compounds. Spirulina and Chlorella are the most popular microalgal species and are marketed as healthy food supplements. At the same time, Amphora holds potential as a source of healthy lipids and essential fatty acids. Yet, there are considerable variations in their reported chemical composition, and less is known about their compositional differences. A multiplexed metabolomic approach was adopted for the quality control (QC) of Spirulina supplements and to compare its constitutive metabolome to Chlorella and Amphora. The adopted protocol comprised gas chromatography-mass spectrometry (GC-MS), ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-HRMS/MS), and ultraviolet-visible spectrophotometry (UV/Vis) for mapping their primary and secondary metabolome. Interestingly, UPLC-HRMS/MS analysis delineated the abundance of fatty acids in Amphora versus glycolipids enrichment in Spirulina, and porphyrins were the main pigments identified in Spirulina, with scarce occurrence in Chlorella. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) analysis of GC-MS data set revealed palmitic acid, 3-mannobiose, and glyceryl-glycoside as being most enriched in Spirulina, versus sucrose and leucine in Chlorella and Amphora, respectively. Despite being of low discriminatory potential, UV/Vis OPLS-DA modeling showed that Spirulina was distinguished with the UV absorbances of carotenoids and chlorophyll pigments, as indicated by its OPLS-DA derived S-plot. Our study provides a QC approach for the analysis of the microalgal species and poses alternative spectral and compositional markers for their discrimination.

Untargeted metabolomics-based molecular networking for chemical characterization of selected Apiaceae fruit extracts in relation to their antioxidant and anti-cellulite potentials.

Stress, obesity, hormonal changes, and aging have been connected to cellulite aggravation resulting in skin dimpled appearance, a very common painless skin disorder with a female preponderance. Several Apiaceae plants have been traditionally used for cosmetic applications. However, their screening for anti-cellulite potential has not been deeply investigated. In this work, UPLC-HRMS/MS coupled with molecular networking was employed to glean a holistic overview of the chemodiversity of the metabolome of nine Apiaceae fruits. Additionally, the extracts were screened for in vitro antioxidant and anti-cellulite activities. Apium graveolens and Petroselinum crispum revealed excellent free radical scavenging activity, remarkably increased lipolysis, and decreased adipogenesis. Furthermore, apigenin and its glycosides were identified to be the major components in both extracts, which might be responsible for the antioxidant activity and anti-cellulite potential. Conclusively, these results signify the potent antioxidant and anti-cellulite properties of A. graveolens and P. crispum fruit extracts, holding potential for the development of plant derived products for cellulite management.

Integrative application of silicon and/or proline improves Sweet corn (Zea mays L. saccharata) production and antioxidant defense system under salt stress condition.

Silicon (Si) and/or proline (Pro) are natural supplements that are considered to induce plants' stress tolerance against various abiotic stresses. Sweet corn (Zea mays L. saccharata) production is severely afflicted by salinity stress. Therefore, two field tests were conducted to evaluate the potential effects of Si and/or Pro (6mM) used as seed soaking (SS) and/or foliar spray (FS) on Sweet corn plant growth and yield, physio-biochemical attributes, and antioxidant defense systems grown in a saline (EC = 7.14dS m-1) soil. The Si and/or Pro significantly increased growth and yield, photosynthetic pigments, free proline, total soluble sugars (TSS), K+/Na+ratios, relative water content (RWC), membrane stability index (MSI), α-Tocopherol (α-TOC), Ascorbate (AsA), glutathione (GSH), enzymatic antioxidants activities and other anatomical features as compared to controls. In contrast, electrolytes, such as SS and/or FS under salt stress compared to controls (SS and FS using tap water) were significantly decreased. The best results were obtained when SS was combined with FS via Si or Pro. These alterations are brought about by the exogenous application of Si and/or Pro rendering these elements potentially useful in aiding sweet corn plants to acclimate successfully to saline soil.

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

HPLC-ESI- MS/MS analysis of beet (Beta vulgaris) leaves and its beneficial properties in type 1 diabetic rats.

The phenolic profile of the leaves of Beta vulgaris subspecies vulgaris variety rubra was investigated by high-performance liquid chromatography (HPLC) coupled to electrospray ionization high resolution mass spectrometric (ESI-HRMS-MS) detection. Mass spectrometry-based molecular networking was employed to dereplicate the known compounds. Twelve known compounds, seven of which are previously undescribed as constituents in the B. vulgaris leaves were dereplicated and assigned with various levels of identification confidence. The ameliorative effects of the aqueous methanolic extract of the leaves were assessed against alloxan induced diabetic rats. It was found that the extract significantly decreased (p < 0.001) serum glucose, lipid profile, ALT, AST, TNF-α, IL-1ß, IL-6, and hepatic MDA levels; and significantly increased (p < 0.001) hepatic TAO and GSH; and down-regulated the expression of hepatic NF-κB versus the untreated diabetic groups, in a dose-dependent manner. In molecular docking, all identified compounds exhibited good glide score against the PPAR-É£ target, confirming the in vivo observed activities. In conclusion, B. vulgaris has immunomodulatory / antioxidant effects that could be helpful in slowing the progression of diabetic complications.

Measuring coordination of epilepsy care: A mixed methods evaluation of social network analysis versus relational coordination.

OBJECTIVES: Coordination of multidisciplinary care is critical to address the complex needs of people with neurological disorders; however, quality improvement and research tools to measure coordination of neurological care are not well-developed. This study explored and compared the value of social network analysis (SNA) and relational coordination (RC) in measuring coordination of care in a neurology setting. The Department of Veterans Affairs Healthcare System (VA) established an Epilepsy Centers of Excellence (ECOE) hub and spoke model of care, which provides a setting to measure coordination of care across networks of providers. METHODS: In a parallel mixed methods approach, we compared coordination of care of VA providers who formally engage the ECOE system to VA providers outside the ECOE system using SNA and RC. Coordination of care scores were compiled from provider teams across 66 VA facilities, and key informant interviews of 80 epilepsy care team members were conducted concurrently to describe the quality of epilepsy care coordinating in the VA healthcare system. RESULTS: On average, members of healthcare teams affiliated with the ECOE program rated quality of communication and respect higher than non-ECOE physicians. Connectivity between neurologist and primary care providers as well as between neurologists and mental health providers were higher within ECOE hub facilities compared to spoke referring facilities. Key informant interviews reported the important role of formal and informal programming, social support and social capital, and social influence on epilepsy care networks. CONCLUSION: For quality improvement and research purposes, SNA and RC can be used to measure coordination of neurological care; RC provides a detailed assessment of the quality of communication within and across healthcare teams but is difficult to administer and analyze; SNA provides large scale coordination of care maps and metrics to compare across large healthcare systems. The two measures provide complimentary coordination of care data at a local as well as population level. Interviews describe the mechanisms of developing and sustaining health professional networks that are not captured in either SNA or RC measures.

Long-term functional outcome and quality of life in patients with high imperforate anus.

PURPOSE: Anorectal malformations (ARMs) are associated with a large number of functional sequale that may affect a child's long-term quality of life (QOL). The purposes of this study were to better quantify patient functional stooling outcome and to identify how these outcomes related to the QOL in patients with high imperforate anus. METHODS: Forty-eight patients from 2 children's hospitals underwent scoring of stooling after 4 years of life. Scoring consisted of a 13-item questionnaire to assess long-term stooling habits (score range: 0-30, worst to best). These results were then correlated with a QOL survey as judged by a parent or guardian. RESULT: Mean (SD) age at survey was 6.5 (1.6) years. Comparison of QOL and clinical scoring showed no signficant difference between the 2 institutions (P > .05). There was a direct correlation between the QOL and stooling score (Pearson r(2) = 0.827; beta coefficient = 24.7, P < .001). Interestingly, functional stooling scores worsened with increasing age (Pearson r(2) = 0.318, P = .02). Patients with associated congenital anomalies had a high rate of poor QOL (44% in poor range; P = .001). Stooling scores decreased significantly with increasing severity/complexity of the ARM (P = .001). CONCLUSION: A large number of children experience functional stooling problems, and these were directly associated with poor QOL. In contrast to previous perceptions, our study showed that stooling patterns are perceived to worsen with age. This suggests that children with ARMs need long-term follow-up and counseling.

Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines.

Transport system x(c)(-) is a member of plasma membrane heterodimeric amino-acid transporters and consists of two protein components, xCT and 4F2hc. This system mediates cystine entry coupled with the exodus of intracellular glutamate and regulates the intracellular glutathione (GSH) levels in most mammalian cultured cells. We studied the activity of system x(c)(-) and GSH content in human ovarian cancer cell line (A2780) and its cisplatin (CDDP)-resistant variant (A2780DDP). The rate of cystine uptake was approximately 4.5-fold higher in A2780DDP cells than in A2780 cells and the cystine uptake in A2780DDP cells was mediated by system x(c)(-). Intracellular GSH content was much higher in A2780DDP cells but it fell drastically in the presence of excess glutamate, which inhibited the cystine uptake competitively. xCT and 4F2hc mRNAs were definitely expressed in A2780DDP cells, but far less in A2780 cells. Expression of system x(c)(-) activity by transfection with cDNAs for xCT and 4F2hc made A2780 cells more resistant to CDDP. Similar results on the cystine uptake were obtained in human colonic cancer cell lines. These findings suggest that the system x(c)(-) plays an important role in maintaining the higher levels of GSH and consequently in CDDP resistance in cancer cell lines.

Sarcoidosis associated with psoriasis vulgaris.

We report a 70-year-old patient with sarcoidosis associated with psoriasis vulgaris. He had a nodule on the medial lower lid of his right eye. Oral corticosteroid for the sarcoid lesions and oral PUVA for psoriasis were employed. The cutaneous lesion disappeared within two months after starting the therapy. No relapse of sarcoidosis has been seen for eight years. The association of sarcoidosis with psoriasis has been previously reported; however, it is still unclear whether this association coincidental or meaningful.

[Efficacy of stress management classes at a health center].

Although interest in mental health promotion has recently been increasing, the most appropriate approaches remain to be determined. Therefore we conducted Stress Management Classes (SMCs) at Higashi Osaka City Naka Health Center in an attempt to help residents to improve their mental health. The purpose of this study was to evaluate the efficacy of SMCs, held four times over 2 months, with an educational program including the concept of stress and instruction in autogenic training as a relaxation technique. Subjects who attended a Health Promotion Class (HPC) at Osaka Prefectural Kaizuka Health Center were used as controls for the study. The aim of the HPC was to prevent chronic physical diseases such as hypertension, diabetes, and hyperlipidemia, with the program consisting mainly of exercise once a week for 3 months. The results were as follows: 1) People who attended SMCs were more likely to have mental health problems than those who attended the HPC. As a result, mentally ill patients could be diagnosed and receive psychiatric treatment at an early stage in the SMC group. 2) Both SMC and HPC attenders reported improvement of their mental health status with the use of POMS (Profile of Mood States). 3) Both SMC and HPC attenders exhibited significant decrease of blood pressure. Although attenders of both classes improved their mental health status, it is important to be able to attract individuals who are in a poor mental condition in case of mental health promotion. In this trial, we found that the term "stress management" was very useful because people who suffered stress were likely to be interested in it. After the Community Health Law was established in 1994, the flow of community health activities has been shifting from the prefectural government to the municipality. However, promoting mental health and welfare is still mainly the role of the prefectural government. In this sense, health centers are appropriate institutions to hold classes as in this trial.

Myofascial pain in patients with postthoracotomy pain syndrome.

OBJECTIVE: Postthoracotomy pain syndrome is generally considered to be neuropathic pain due to intercostal nerve injury. However, nonneuropathic pain can also occur following thoracic surgery. We present a series of cases with postthoracotomy pain syndrome in which myofascial pain was thought to be a causative component of postthoracotomy pain syndrome. CASE REPORT: Twenty-seven patients (17 men and 10 women) were treated with trigger point injections, intercostal nerve blocks, and/or epidural blocks. Clinical criteria were used to diagnose the myofascial pain. A visual analogue scale was used, and sensory disturbances were recorded before and after treatment. A trigger point in a taut muscular band within the scapular region, which we diagnosed as myofascial pain, was observed in 67% of the patients. The existence of this trigger point significantly increased the rate of success for the treatments. CONCLUSIONS: Postthoracotomy pain may result, at least in part, from a nonneuropathic origin (myofascial pain). It is recommended that each patient be examined in detail to determine whether there is a trigger point in a taut muscular band within the scapular region. If found, this point is suggested as a good area for anesthetic injection.

[Cooperative study of intraarterial preventive chemotherapy after resection of hepatic metastasis from colorectal cancer].

This is a compilation of the results of preventive intraarterial infusion following resection of hepatic metastasis from colorectal cancer at four surgical centers. The cases studied included two groups: A) 76 patients who underwent normal liver resection only, and B) 78 patients who underwent resection with adjuvant chemotherapy. Methods included: 1) WHF, 50 cases; 2) other methods using 5-FU, 18 cases; and 3) intraarterial infusions other than 5-FU, 10 (2 cases, outcome unknown). Survival rates for groups A and B for 1 and 5 years were 71.2, 18.9% and 91.5, 56.2%, respectively, with the rates for the intraarterial infusion group showing far better results. The 1- and 5-year survival rates in terms of infusion methods were: 1) 90.7% and 64.6%; 2) 94.4% and 39.3%; and 3) 90% and 60%, respectively, showing no remarkable differences between methods. Total doses of 5-FU were (a) less than 5 g, 7 patients (b) 5-15 g, 16 patients (c) 15-30 g, 22 patients (d) greater than 30 g, 23 patients. A comparison of 1- and 5-year survival rates shows (a) 85.7% and 17.1%; (b) 66.5% and 44.3%; (c) 100% and 62.7%; (d) 100% and 66.5%, respectively, with doses (c) and (d) showing markedly better results than the (a) dosage. From this we conclude that the group undergoing intraarterial hepatic infusion had a markedly improved prognosis compared to the group not undergoing any type of adjuvant therapy. Also, groups receiving a dosage of 15 g or greater of 5-FU showed prolonged survival rates.

Multi-enzymatic glucosylation using Eucalyptus UDP-glucosyltransferase coupled UDPglucose-fermentation by bakers' yeast.

The enzymatic synthesis of glucoside compounds using a membrane-associated UDP-glucosyltransferase fraction from Eucalyptus perriniana cultured cells as a water-insoluble catalyst (N. Nakajima, et. al., J. Ferment. Bioeng., 84 (5), pp. 455-460, 1997) has been effectively done by coupling UDPglucose-fermentation by bakers' yeast. For example, beta-thujaplicin (hinokitiol) and p-aminobenzoic acid were converted respectively to their corresponding beta-D-monoglucosides with the conversion rate of around 24-26% by the multi-enzymatic system with UDPglucose as a glucose donor, which is produced by yeast cells from glucose and 5'-UMP. Addition of either cellobiose, a substrate of beta-glucosidase, or DL-1,2-anhydro-myo-inositol, an inhibitor for the enzyme in the reaction mixture, could increased the yield of these beta-D-monoglucosides. This new enzymatic system could also be used for the synthesis of flavonoid glucosides such as isoquercitrin (quercetin 3-O-beta-D-glucoside).

Relationship of coffee consumption with serum lipids and lipoproteins in Japanese men.

PURPOSE: To examine the relationship of instant coffee and brewed coffee with serum lipids and lipoproteins in Japanese men. METHODS: Study subjects were 4587 male self-defense officials aged 48-56 years who had a preretirement health examination at one of the three hospitals of the Self-Defense Forces from October 1986 to December 1992. A self-administered questionnaire ascertained lifestyle characteristics including consumption of a limited number of foods and beverages by all of the men. Serum concentrations of total cholesterol (TC), triglycerides (TG), and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol levels were calculated from the values of TC, TG, and HDL cholesterol. RESULTS: While the consumption of brewed coffee was unrelated to any parameter of serum lipids and lipoproteins, instant coffee consumption showed a highly significant positive association with serum LDL cholesterol levels and an inverse association with serum TG levels. After adjustment for body mass index, smoking, alcohol use, green tea consumption, rank, and hospital, for each cup of instant coffee per day, LDL cholesterol levels were 0.82 mg/dl (95% confidence interval (CI) 0.29-1.35) higher, and TG levels in a natural log-scale were 0.014 mg/dl (95% CI 0.006-0.022) lower. There was also a tendency for a positive association between instant coffee intake and serum TC levels (trend p = 0.09). HDL cholesterol levels were unrelated to instant coffee consumption. These associations did not change after additional adjustment for selected foods and beverages associated with serum lipids and lipoproteins. CONCLUSIONS: The findings suggest that instant coffee, not brewed coffee, may be associated with raised levels of serum LDL cholesterol and decreased levels of serum TG.

Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males.

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2.3 and 3.1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0.0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

[Intra-arterial preventive chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer].

We treated 18 cases with intra-hepatic arterial infusion chemotherapy after resection of hepatic metastasis from colorectal cancer (June 1991-September 1997). Eight cases were H1, 7 were H2, and 3 were H3. Hepatic lobectomy was done in 3 cases, lobectomy + partial resection in 2 cases, and partial resection in 13 cases. All cases received high-dose intermittent 5-FU infusion (WHF = 5-FU 1,000 mg/m2/5 hrs/w) on an outpatient basis. The total frequency of WHF was 4-54 times (average 29), and total 5-FU doses ranged from 6.0 to 81.0 g (average 40 g). The 1- and 5-year cumulative survival rates were 100% and 77.5% in all patients 100% and 87.5% in H1 group and 100% and 64.3% in H2 + H3 group, respectively. There was no significant difference of survival between the H1 and H1 + H3 groups. The 1- and 5-year recurrence rates in residual liver were 5.9% and 14.4%, respectively. One of 2 cases with residual liver recurrence was resected for metastasis again, and the patient is now in a disease-free state. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect for their survival, not only in H1 group but also in H2 + H3 group.

[Complication due to arterial infusion chemotherapy for liver metastasis from colorectal cancer].

OBJECTIVES: Arterial infusion chemotherapy is considered to be an extremely effective treatment for liver metastasis from colorectal cancer in terms of its tumor reduction and preventing recurrence in residual liver after resection. However, there still remain some unclear points as to the influence on hepatic artery and bile duct when this treatment is used over the long term. We report some conclusions obtained by examining cases of hepatic arterial occlusion (stenosis) and biliary complication who received this treatment. MATERIALS AND METHODS: Thirty-six cases who received this treatment over 3 months were the objects of this study, with the aim of direct effect against metastatic focus (21 cases) and prevention of recurrence in residual liver (15 cases). The ages were from 27 to 81; 22 cases were male and 14 were female. Indwelling routes of catheter were gastroduodenal artery (GDA) in 28 cases and femoral artery (FA) in 8 cases. Intermittent high-dose infusion (WHF: 5-FU 1,000 mg/m2/5 hrs qw) was adopted as the method. RESULTS: Hepatic arterial occlusion or stenosis was observed in 12 cases (GDA: 10; FA: 2). There seemed to be no correlation with the total dosage of 5-FU or the number of administrations. Even when hepatic arterial occlusion or stenosis occurred, no change was observed in liver function, and there no death was caused by this. However, CT showed a low-density area followed by atrophy in the right lobe in one case with right hepatic arterial stenosis, despite normal portal blood flow. Of the 6 cases which developed obstructive jaundice, 4 were due to the increase of metastatic focus or lymph nodes, and 1 case without dilatation of bile duct died from suspected sclerosing cholangitis. In this case, ALP had been increasing since 1 month before the onset of jaundice. Another case which developed biloma accompanied by the increase of serum bilirubin improved by discontinuance of chemotherapy. CONCLUSION: Since arterial infusion chemotherapy for liver metastasis from colorectal cancer causes hepatic arterial occlusion (stenosis) at a high rate, early detection of abnormalities by liver function test and imaging diagnosis which leads to early treatment is important.

Cardiac beta-adrenergic signaling pathway alteration in isoproterenol-induced cardiac hypertrophy in male Sprague-Dawley rats.

Isoproterenol was continuously administered to rats at a rate of 2.5 microg/kg/min for 7 days via subcutaneously implanted osmotic minipumps. This treatment induced cardiac hypertrophy with increases in heart rate and systolic blood pressure. Beta-adrenoceptor (beta-AR) density decreased in hypertrophied hearts, but the affinity for 125I-cyanopindolol did not change. The beta-AR density decrease did not accompany the change in expression of beta1-AR mRNA. In hypertrophied hearts, adenylyl cyclase activities in the steady state, and stimulated with isoproterenol, forskolin, and manganese, decreased but there was no change in the expression of adenylyl cyclase type V mRNA. The results suggest that beta-AR downregulation and adenylyl cyclase desensitization in isoproterenol-induced cardiac hypertrophy are caused by post-transcriptional changes.

A case of chromomycosis with tumor-like growth.

A 66-year-old woman who lived on Tokunoshima Island, a small and remote southern island of the Japanese archipelago, had suffered from chromomycosis for more than 30 years and presented with a tumor-like growth on the posterior crural region of his right leg. Fonsecaea pedrosoi was identified as the pathogen from its growth pattern and micromorphological characteristics. The patient was successfully treated with 5-fluorocytosine, itoraconazole, and topical thermotherapy.