Piperine, an active ingredient of white pepper, suppresses the growth of multidrug-resistant toxigenic Vibrio cholerae and other pathogenic bacteria.

Emergence and rapid spread of multidrug-resistant (MDR) bacteria including Vibrio cholerae are a global public health issue. Much attention has been paid to natural compounds, such as spices and herbs to find novel antimicrobial compounds as they are considered to be cheaper alternatives to develop as a drug. Here, we show that methanol extract of white pepper could inhibit the growth of V. cholerae O1 El Tor variant, responsible for the recent outbreaks/epidemics. Furthermore, we demonstrate for the first time that piperine, the major component of white pepper, showed a dose-dependent bactericidal effect on V. cholerae growth irrespective of their biotypes and serogroups in the presence of 200 and 300 µg ml-1 of piperine, respectively. Piperine also inhibited the growth of MDR strains of Pseudomonas aeruginosa, Escherichia coli isolated from poultry and enterohemorrhagic/enteroaggregative E. coli O104 in the presence of 200 µg ml-1 . Interestingly, we did not observe any significant inhibitory effect of piperine on E. coli strains isolated from healthy person even up to 200 µg ml-1 . Our data suggest that piperine could be a novel antimicrobial agent in therapeutic and preventive applications against infections caused by pathogenic bacteria including MDR strains.

Tea crude extracts effectively inactivate severe acute respiratory syndrome coronavirus 2.

It is well known that black and green tea extracts, particularly polyphenols, have antimicrobial activity against various pathogenic microbes including viruses. However, there is limited data on the antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged rapidly in China in late 2019 and which has been responsible for coronavirus disease 2019 (COVID-19) pandemic globally. In this study, 20 compounds and three extracts were obtained from black and green tea and found that three tea extracts showed significant antiviral activity against SARS-CoV-2, whereby the viral titre decreased about 5 logs TCID50 per ml by 1·375 mg ml-1 black tea extract and two-fold diluted tea bag infusion obtained from black tea when incubated at 25°C for 10 s. However, when concentrations of black and green tea extracts were equally adjusted to 344 µg ml-1 , green tea extracts showed more antiviral activity against SARS-CoV-2. This simple and highly respected beverage may be a cheap and widely acceptable means to reduce SARS-CoV-2 viral burden in the mouth and upper gastrointestinal and respiratory tracts in developed as well as developing countries.

Chlorine dioxide is a more potent antiviral agent against SARS-CoV-2 than sodium hypochlorite.

BACKGROUND: A new coronavirus (SARS-CoV-2) abruptly emerged in Wuhan, China, in 2019 and rapidly spread globally to cause the COVID-19 pandemic. AIM: To examine the anti-SARS-CoV-2 activity of the potent disinfectant Cleverin, the major disinfecting component of which is chlorine dioxide (ClO2); and to compare the results with that of sodium hypochlorite in the presence or absence of 0.5% or 1.0% foetal bovine serum (FBS). METHODS: Concentrated SARS-CoV-2 viruses were treated with various concentrations of ClO2 and sodium hypochlorite and 50% tissue culture infective dose was calcurated to evaluate the antiviral activity of each chemical. FINDINGS: When SARS-CoV-2 viruses were treated with 0.8 ppm ClO2 or sodium hypochlorite, viral titre was decreased only by 1 log10 TCID50/mL in 3 min. However, the viral titre was decreased by more than 4 log10 TCID50/mL when treated with 80 ppm of each chemical for 10 s regardless of presence or absence of FBS. It should be emphasized that treatment with 24 ppm of ClO2 inactivated more than 99.99% SARS-CoV-2 within 10 s or 99.99% SARS-CoV-2 in 1 min in the presence of 0.5% or 1.0% FBS, respectively. By contrast, 24 ppm of sodium hypochlorite inactivated only 99% or 90% SARS-CoV-2 in 3 min under similar conditions. Notably, except for ClO2, the other components of Cleverin such as sodium chlorite, decaglycerol monolaurate, and silicone showed no significant antiviral activity. CONCLUSION: Altogether, the results strongly suggest that although ClO2 and sodium hypochlorite are strong antiviral agents in absence of organic matter but in presence of organic matter, ClO2 is a more potent antiviral agent against SARS-CoV-2 than sodium hypochlorite.

Herd prevalence of Enterobacteriaceae producing CTX-M-type and CMY-2 ß-lactamases among Japanese dairy farms.

AIMS: To determine the herd prevalence of Enterobacteriaceae producing CTX-M-type extended-spectrum ß-lactamases (ESBLs) among 381 dairy farms in Japan. METHODS AND RESULTS: Between 2007 and 2009, we screened 897 faecal samples using BTB lactose agar plates containing cefotaxime (2 µg ml(-1)). Positive isolates were tested using ESBL confirmatory tests, PCR and sequencing for CTX-M, AmpC, TEM and SHV. The incidence of Enterobacteriaceae producing CTX-M-15 (n = 7), CTX-M-2 (n = 12), CTX-M-14 (n = 3), CMY-2 (n = 2) or CTX-M-15/2/14 and CMY-2 (n = 4) in bovine faeces was 28/897 (3·1%) faecal samples. These genes had spread to Escherichia coli (n = 23) and three genera of Enterobacteriaceae (n = 5). Herd prevalence was found to be 20/381 (5·2%) dairy farms. The 23 E. coli isolates showed clonal diversity, as assessed by multilocus sequence typing and pulsed-field gel electrophoresis. The pandemic E. coli strain ST131 producing CTX-M-15 or CTX-M-27 was not detected. CONCLUSIONS: Three clusters of CTX-M (CTX-M-15, CTX-M-2, CTX-M-14) had spread among Japanese dairy farms. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the prevalence of multidrug-resistant CTX-M-15-producing E. coli among Japanese dairy farms.

A new predictive indicator for development of pressure ulcers in bedridden patients based on common laboratory tests results.

BACKGROUND: Various scales have been devised to predict development of pressure ulcers on the basis of clinical and laboratory data, such as the Braden Scale (Braden score), which is used to monitor activity and skin conditions of bedridden patients. However, none of these scales facilitates clinically reliable prediction. AIMS: To develop a clinical laboratory data-based predictive equation for the development of pressure ulcers. METHODS: Subjects were 149 hospitalised patients with respiratory disorders who were monitored for the development of pressure ulcers over a 3-month period. The proportional hazards model (Cox regression) was used to analyse the results of 12 basic laboratory tests on the day of hospitalisation in comparison with Braden score. RESULTS: Pressure ulcers developed in 38 patients within the study period. A Cox regression model consisting solely of Braden scale items showed that none of these items contributed to significantly predicting pressure ulcers. Rather, a combination of haemoglobin (Hb), C-reactive protein (CRP), albumin (Alb), age, and gender produced the best model for prediction. Using the set of explanatory variables, we created a new indicator based on a multiple logistic regression equation. The new indicator showed high sensitivity (0.73) and specificity (0.70), and its diagnostic power was higher than that of Alb, Hb, CRP, or the Braden score alone. CONCLUSIONS: The new indicator may become a more useful clinical tool for predicting presser ulcers than Braden score. The new indicator warrants verification studies to facilitate its clinical implementation in the future.

Evaluation of engraftment after single islet transplantation from a brain-dead donor by the secretory unit of islet transplant objects (SUITO) index.

BACKGROUND: Evaluation of engraftment is important to assess the success of islet transplantation. Recently, we developed a simple index of islet engraftment, the secretory unit of islet transplant objects (SUITO) index. The formula is: 1500 x fasting C-peptide level [ng/dL]/(fasting blood glucose levels [mg/dL]-63). A SUITO index of more than 26 was associated with insulin independence. MATERIALS AND METHODS: In this study, we compared islet engraftment efficacy using the SUITO index after a single infusion of islets from brain-dead donors into 6 recipients. We calculated the SUITO index from postoperative days 3 to 30. We compared the insulin reduction rate with the SUITO index and islet equivalent per kilogram body weight (IE/Kg). We also measured the level of glycosylated hemoglobin (HbA 1C) at 3 months posttransplantation to assess glycemic control after islet transplantation. RESULTS: In 5 cases, islets were cultured before transplantation and in 1 case they were transplanted without culture. Without culture, the SUITO index and insulin reduction rate were highest. The SUITO index significantly correlated with the insulin reduction rate (P = .031, R2 = .728), but the IE/kg was not significantly correlated (P = .303) with the rate of insulin reduction. All cases showed improved HbA 1C to the normal range. CONCLUSIONS: Immediate transplantation without culture substantially improved the efficacy of engraftment of transplanted islets. The SUITO index was a better predictor than islet mass per body weight for clinical outcomes.

Estimation of donor usability for islet isolation with the modified Ricordi method.

BACKGROUND: The quality of donor pancreata is important for successful islet isolation. However, in some countries like Japan, the number of donor pancreata is low. Therefore, marginal donor pancreata have been used with less restrictive donor criteria. In order to use marginal donor pancreata, we established the modified Ricordi method. According to the United Network for Organ Sharing (UNOS) in 2005, more than 6000 pancreata were not clinically usable in the United States. In this study, we reevaluated donor usability based on the Japanese islet donor criteria. MATERIALS AND METHODS: We reviewed donor charts with well-documented cases in Texas from 2005 to 2006. We counted the number of pancreata for pancreas transplantation or islet transplantation. If not used clinically, the reason was also reviewed. Donors were reevaluated based on the Japanese islet donor criteria. RESULTS: We reviewed 236 donor charts, including 29 pancreata used for whole pancreas transplantations and 13 for islet isolation; therefore, 194 pancreata were not used. Among the 194 cases, we were able to identify the reasons that the pancreata were not used in 186 cases. When we applied the Japanese acceptance criteria, an additional 82 of 186 cases (44%) seemed suitable for islet isolations. CONCLUSIONS: With the modified Ricordi method, more than 2500 donor pancreata might be used for islet isolation in the United States when the Japanese criteria are applied.

Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys.

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.

Induction of cytochrome P450 1B1 in lung, liver and kidney of rats exposed to diesel exhaust.

We have shown previously that diesel exhaust particle (DEP) extracts (DEPE) and 1-nitropyrene were genotoxically activated by human cytochrome P450 1B1 in SOS/umu assay. In this study, the in vivo induction of P450 family 1 enzymes in rats by exposure to diesel exhaust was investigated with regard to mRNA levels, P450 enzyme content, drug oxidation activities in the microsomes and umu gene expression of typical P450 substrates and DEPE itself catalyzed by the microsomes. Male Fischer 344 rats (4 weeks old) were exposed to 0.3 and 3.0 mg/m(3) DEP for 12 h per day for 4 weeks; the former dose corresponded to the typical daily airborne particle concentration. The levels of mRNA of rat P450 1B1 and P450 1A1 in the lung and liver were significantly increased 1.1-1.4-fold by exposure to 0.3 mg/m(3) DEP. Diesel exhaust particle extracts induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of a functional P450 system and were further activated by human recombinant P450 1B1. Using an O-acetyltransferase overexpressing Salmonella strain, genotoxic activation of P450 1B1 marker chemicals (1-nitropyrene, 1-aminopyrene and DEPE) by lung, liver and kidney microsomes was increased 1.7-4.2-, 1.4-1.5- and 1.0-1.3-fold, respectively, by exposure to 0.3 mg/m(3) DEP. Activation of 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1; marker for P450 1A1) by lung microsomes and the P450 1A2 content in liver microsomes were slightly increased by exposure to 3.0 mg/m(3) DEP. This is the first report to suggest that typical daily contaminant levels (0.3 mg particle/m(3)) of diesel exhaust can induce P450 1B1 in rats and that the induced P450 1B1 may catalyze the genotoxic activation of DEP.

Metabolic activation of carcinogenic 1-nitropyrene by human cytochrome P450 1B1 in Salmonella typhimurium strain expressing an O-acetyltransferase in SOS/umu assay.

Metabolic activation of 1-nitropyrene (1-NP) by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes was investigated. 1-NP induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of any P450 system, but the activities were influenced by the levels of bacterial O-acetyltransferase (OAT) and nitroreductase. Metabolic activation of 1-NP by human P450 1B1/NPR membranes was observed and was influenced by the levels of OAT levels in tester strains. Metabolic activation of 1-NP (0.3microM) by P450 1B1 was 750 umu units/min/nmol P450 1B1 in an OAT-overexpressing strain NM2009. The metabolic activation of 1-NP (3-30microM) was similar (approximately 300 umu units/min/nmol P450 1B1) using TA1535/pSK1002 or OAT-deficient strain NM2000. P450 1B1 had the highest catalytic activities among P450 family 1 enzymes for the activation of 1-aminopyrene (1-AP) in the OAT-overexpressing strain NM2009, suggesting nitrenium ion formation via N-hydroxylation/O-acetylation. High-performance liquid chromatography (HPLC) analyses revealed the formation of 1-nitropyrene-6-ol and also 1-nitropyrene-3-ol, 1-nitropyrene-8-ol, and trans-4,5-dihydroxy-4,5-diol-1-nitropyrene from 1-NP (10microM), catalyzed by P450 1B1. These results indicate that 1-NP can be activated by human P450 1B1 to a genotoxic agent by nitroreduction/O-acetylation at low substrate concentrations and probably by epoxidation (independent of OAT) at high concentrations.

Distribution of median, ulnar and radial motoneurons in the monkey spinal cord: a retrograde triple-labeling study.

Topographic distribution of motoneurons innervating hand muscles through the median (Mn), ulnar (Ul), or radial (Rd) nerves was examined using a retrograde multiple-labeling technique in the macaque monkey. The Mn and Ul motoneurons, i.e. flexor motoneurons, were distributed from C6 to T2 and from C7 to T2 segments of the spinal cord, respectively, while the Rd motoneurons, i.e. extensor motoneurons, were distributed from C4 to T2. The present study further revealed partial intermingling of the cell bodies and partial overlap of the dendritic fields among the motoneurons projecting through different nerves, indicating that subregions of motoneuronal pool participate in coordination between the flexor and extensor, or among the flexor muscles. It was suggested that there exists a control mechanism for precise hand movements in the spinal cord.

Somatotopic arrangement and corticocortical inputs of the hindlimb region of the primary motor cortex in the macaque monkey.

Using Japanese monkeys, we examined the somatotopic organization of the hindlimb region of the primary motor cortex (MI) with intracortical microstimulation. In the hindlimb region of the MI, areas representing distal movements (digits and ankle joints) were basically surrounded by those representing proximal movements (knee and hip joints). Thus, the hindlimb region of the MI has a nested or horseshoe-like somatotopic representation. We then examined the topographic organization of corticocortical projections to the hindlimb region of the MI by the retrograde double-labeling technique: one monkey received paired injections of Fast blue (FB) and Diamidino yellow (DY) into hindlimb or forelimb representation of the MI, respectively, while two monkeys received those of FB and DY into proximal or distal representation of the hindlimb region of the MI, respectively. The neurons projecting to the hindlimb region of the MI were located in cortical areas largely separate from those projecting to the forelimb region of the MI. On the other hand, we found a substantial overlap of corticocortical neurons projecting to the proximal and distal parts of the hindlimb region of the MI in the dorsal division of the premotor cortex and the cingulate motor areas.

Organization of inputs from cingulate motor areas to basal ganglia in macaque monkey.

The cingulate motor areas reside within regions lining the cingulate sulcus and are divided into rostral and caudal parts. Recent studies suggest that the rostral and caudal cingulate motor areas participate in distinct aspects of motor function: the former plays a role in higher-order cognitive control of movements, whereas the latter is more directly involved in their execution. Here, we investigated the organization of cingulate motor areas inputs to the basal ganglia in the macaque monkey. Identified forelimb representations of the rostral and caudal cingulate motor areas were injected with different anterograde tracers and the distribution patterns of labelled terminals were analysed in the striatum and the subthalamic nucleus. Corticostriatal inputs from the rostral and caudal cingulate motor areas were located within the rostral striatum, with the highest density in the striatal cell bridges and the ventrolateral portions of the putamen, respectively. There was no substantial overlap between these input zones. Similarly, a certain segregation of input zones from the rostral and caudal cingulate motor areas occurred along the mediolateral axis of the subthalamic nucleus. It has also been revealed that corticostriatal and corticosubthalamic input zones from the rostral cingulate motor area considerably overlapped those from the presupplementary motor area, while the input zones from the caudal cingulate motor area displayed a large overlap with those from the primary motor cortex. The present results indicate that a parallel design underlies motor information processing in the cortico-basal ganglia loop derived from the rostral and caudal cingulate motor areas.

Bioactivation of diesel exhaust particle extracts and their major nitrated polycyclic aromatic hydrocarbon components, 1-nitropyrene and dinitropyrenes, by human cytochromes P450 1A1, 1A2, and 1B1.

The genotoxicities of four samples of diesel exhaust particle (DEP) extracts (DEPE) and nine nitroarenes found in DEPE were investigated after activation catalyzed by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes. The DEPE samples induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 without any P450 system and were further activated by human P450 1B1/NPR membranes. Moderate activation of the DEPE sample by P450 1A2/NPR membranes was also observed, but not by either P450 1A1/NPR or NPR membranes. 1-Nitropyrene (1-NP) was strongly activated by human P450 1B1/NPR membranes. 1,8-Dinitropyrene (1,8-DNP) was most highly activated by P450 1A1 and 1B1 systems for the three DNPs tested. In contrast, 1, 3-DNP was inactivated by P450 1A1/NPR, 1A2/NPR, and 1B1/NPR systems and slightly activated by NPR membranes. 2-Nitrofluoranthene (2-NF) and 3-nitrofluoranthene (3-NF) showed activities similar to 1-NP after bioactivation by P450 1B1/NPR membranes. However, the genotoxicities of 6-nitrochrysene, 7-nitrobenz[a]anthracene, and 6-nitrobenzo[a]pyrene were all weak in the present assay system. Apparent genotoxic activities of DEPE were very low compared with standard nitroarenes in the presence of P450s, possibly because unknown component(s) of DEPE had inhibitory effects on the bioactivation of 1-NP and 1,8-DNP catalyzed by human P450 1B1. These results suggest that environmental chemicals existing in airborne DEP, in addition to 1-NP, 1,6-DNP, 1,8-DNP, 2-NF, and 3-NF, can be activated by human P450 1B1. Biological actions of air pollutants such as nitroarenes to human extrahepatic tissues may be of concern in tissues in which P450 1B1 is expressed.

Direct projections from the magnocellular division of the basal nucleus of the amygdala to the principal part of the cortical masticatory area in the macaque monkey.

Direct projections from the amygdala to the cortical masticatory area were found in the macaque monkey. Under the guidance of intracortical microstimulation, retrograde tracers were injected into multiple jaw movement-related regions of the frontal lobe. The cortical masticatory area, especially its principal part, stimulation of which elicited rhythmic jaw movement, was the only site of injection that produced neuronal labeling in the amygdala. The cells of origin of such projections were localized in the medial aspect of the magnocellular division of the basal nucleus through its rostral level. No labeled neurons were observed in the amygdala after tracer injection into any other cortical jaw movement-related region. The present results suggest that the amygdaloid input to the cortical masticatory area may exert some modulatory influence on the generation of masticatory rhythm.

B-mode and color Doppler ultrasound imaging for localization of microelectrode in monkey brain.

Using alert monkeys, we attempted ultrasound imaging after partial craniotomy to localize a metal microelectrode in the brain. B-mode ultrasonography provided images of sulcus and gyrus patterns of the cerebral cortex, and locations of the ventricles and subarachnoid cisterns. As the microelectrode proceeded in the brain, the position of the microelectrode was clearly identified. Electrolytic microlesions generated by delivering direct currents via the microelectrode could also be detected. Color Doppler imaging of blood vessels of the brain was helpful to demarcate deep brain structures and to avoid accidental injury of the blood vessels by the microelectrode. The ultrasonography will make it possible to place recording microelectrodes or injection needles accurately in target regions of the brain in physiological, anatomical or behavioral experiments.

A cortical motor region that represents the cutaneous back muscles in the macaque monkey.

A cortical motor region that represented the cutaneous muscles on the back was identified on the medial wall of the frontal lobe in the macaque monkey. In this region, neurons responded to somatosensory stimuli such as light touch or squeezing of the back skin, and intracortical microstimulation elicited contraction of the back skin. Such a region was located primarily on the dorsal bank of the cingulate sulcus, corresponding to the dorsal cingulate motor area.

Selenium kinetics and changes in glutathione peroxidase activities in patients receiving long-term parenteral nutrition and effects of supplementation with selenite.

Selenium (Se) is an essential trace element in humans. Patients receiving long-term parenteral nutrition (PN) are at risk for Se deficiency. We investigated changes in Se levels and glutathione peroxidase (GSH-Px) activity in serum and tissue (red blood cells, RBC) in addition to urinary excretion of Se in patients receiving long-term PN with and without Se supplementation. In patients without Se supplementation, both Se levels and GSH-Px activity in serum decreased with duration of PN. The serum Se levels were below the lower limits of the control values in 19 of 33 patients (58%) who received PN for less than 1 mo. Conversely, RBC GSH-Px activity remained at a sufficient level in 9 of 12 patients (75%) who received PN for 3-6 mo. The RBC Se levels in all of these patients were lower than the control levels. Urinary Se concentrations were significantly correlated with serum Se concentrations by linear regression analysis (r = 0.707, P < 0.05). In patients with Se supplementation, urinary Se concentrations increased exponentially with increases in serum Se levels. These findings indicate that a time lag precedes the decrease in levels of serum Se, RBC Se, serum GSH-Px, and RBC GSH-Px in patients without Se supplementation and the increase in excretion of urinary Se in patients with Se supplementation. The monitoring of not only serum Se levels but also RBC GSH-Px activity and urinary Se levels is required for optimal Se supplementation during long-term PN.

[A patient with dysphagia treated successfully and discharged without nutritional support].

One of the main targets of medical care provided in our ward, which specializes in the cooperative practice of hospital- and home-doctors, is to maintain the quality of patients' lives after they are discharged from our hospital through home medical care by home-doctors. Intravenous hyperalimentation and tube-feeding at home are suitable solutions for some patients with dysphagia after cerebral infarction. However, the difficulties faced in their management are the burden on the families, which tends to be an obstacle for at-home-practice. We describe herein a case of severe dysphagia treated successfully through our rehabilitation program and discharged without nutritional supports. An 82-year-old man was admitted to our hospital suffering from pyrexia and dysbasia. The man, who lives with his wife and his son's family, was diagnosed with aspiration pneumonia and multiple cerebral infarctions. The test for swallowing reflex revealed an impaired first phase reflex and intravenous hyperalimentation was performed for his nutritional support. He was still suffering from dysphagia but had the desire to eat orally after his dysbasia and aspiration pneumonia were cured. A rehabilitation program was scheduled with the aims of 1) recovery of ingestion and 2) sufficient expectoration, with an ongoing teaching program for the management of intravenous hyperalimentation. After one month of rehabilitation (ice-massaging, muscle rehabilitation of the tongue and neck and expectoration training in a prone position and after gorging), his ability to swallow was gradually recovered. With the frequent confirmation of absence of aspiration, special forms of diets were served and upgraded from jelly, paste-like-food to soft-cooked steamed rice. The patient is now at home without any nutritional support. Nutritional management without intravenous hyperalimentation or tube-feeding is important or even essential for some families providing home-care for patients. The problem of aging requires us to reduce the burden that families (who may be also getting older) should carry. We try to support patients and families for better home-care through cooperation with society and home-doctors.