Biomedical subjects

E Hirayama

Publications and source records attributed to E Hirayama.

At least 19 recordsLinked to original sources

PubMed2001

K252a, an indrocarbazole derivative, causes the membrane of myoblasts to enter a fusion-capable state.

K252a, an indrocarbazole derivative and protein kinase inhibitor, is reported to promote myogenic differentiation in C2 mouse myoblasts. We examined the effects of K252a on QM-RSV cells, quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus. K252a promoted myotube formation of QM-RSV cells. Presumptive QM-RSV cells also formed multinucleated cells when exposed to K252a. However, the expression of myogenin, a muscle regulatory factor, was not stimulated in the presence of the drug, suggesting that it promotes membrane fusion but not myogenic differentiation. To confirm the promotion of membrane fusion by K252a, presumptive C2 cells, which are strongly resistant to HVJ-mediated cell fusion, were fused by HVJ (Sendai virus) after K252a treatment. Presumptive C2 cells treated with K252a fused with HVJ, demonstrating that K252a causes the cells to enter a fusion-capable state. The amount of membrane cholesterol, a factor that decreases membrane fluidity, fell in K252a-treated C2 cells. The results suggest that a decrease of membrane cholesterol is a cause of the change that renders myoblast membrane susceptible to fusion in the presence of K252a.

Animals↗

PubMed2001

Characterization of myogenic cell membrane: spontaneous formation of heterokaryotic myotubes between two different kinds of myoblasts.

In a previous study, it has been shown that presumptive mouse C2 myoblast cells are strongly resistant to HVJ (hemaglutinating virus of Japan, Sendai virus)-mediated cell fusion, but do become capable of fusion upon differentiation. Quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells) also become more sensitive to HVJ-mediated cell fusion during differentiation. Investigations were undertaken to see whether heterokaryotic myotubes were formed spontaneously by co-culture of two different kinds of myogenic cells, QM-RSV cells and C2 cells. When both cells were committed to myotube formation, they spontaneously fused without HVJ on co-culture. On the other hand, when both or one of the cells were in the presumptive state, heterokaryons were not formed by co-culturing. Furthermore, committed QM-RSV cells did not fuse with non-myogenic cells. These results indicate that the membranes of myogenic cells change to become capable of fusion for myotube formation during differentiation.

3T3 Cells↗

PubMed2001

Characterisation of myogenic cell membrane: II. Dynamic changes in membrane lipids during the differentiation of mouse C2 myoblast cells.

Proliferating mouse C2 myoblast cells resist haemagglutinating virus of Japan, Sendai virus (HVJ) mediated cell fusion. However, differentiating C2 cells can be induced to fuse by HVJ, suggesting that the rigid membrane of C2 cells changes during the differentiation. To investigate this phenomenon, changes in membrane lipids which affect fluidity were examined. Membrane cholesterol gradually decreased with the differentiation of C2 cells. However, spontaneous fusion to form myotubes and artificial fusion induced by HVJ were both inhibited when the level of cholesterol was prevented from falling in the cell membrane. The membranes of differentiating C2 cells contained more unsaturated fatty acids than those of proliferating cells. Thus, when differentiating C2 cells were treated with stearate (a saturated fatty acid), they failed to form myotubes and were insensitive to HVJ-mediated fusion. Whereas, if proliferating C2 cells were given linolenate (an unsaturated fatty acid), they became capable of HVJ-induced fusion. These results indicate that differentiating C2 cells change their fusion sensitivity by decreasing cholesterol, probably at the same time as they increase the unsaturated fatty acid content of the cell membrane.

Animals↗

PubMed2001

Ras/MAP kinase pathway is associated with the control of myotube formation but not myofibril assembly in quail myoblasts transformed with Rous sarcoma virus.

Tyrosine kinase activity of v-Src from Rous sarcoma virus (RSV) inhibits the differentiation of quail myoblasts. To clarify the inhibitory mechanism, we focused on the signaling pathways from v-Src. When the activation of the Ras/MAP (mitogen-activated protein) kinase pathway was inhibited by a dominant-negative mutant of Ras or PD98059, a specific inhibitor of p42 MAP kinase kinase, differentiation was restored; muscle specific proteins were expressed and myotubes formed even under active conditions of v-Src. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (P13-kinase), showed no effects on the inhibition by v-Src. These findings suggest that v-Src activates the Ras/MAP kinase signaling pathway, but not the P13-kinase pathway, and inhibits the differentiation. However, the myotubes derived from the dominant-negative Ras did not form actin fibers, suggesting that myofibril assembly is regulated by other pathway(s) from v-Src.

Animals↗

PubMed2001

Characterization of heterokaryons between skeletal myoblasts and somatic cells formed by fusion with HVJ (Sendai virus); effects on myogenic differentiation.

In skeletal myogenic differentiation, myoblasts fuse with myogenic cells spontaneously, but do not fuse with non-myogenic cells either in vivo or in vitro, suggesting that the fusion of myoblasts with non-myogenic cells is unsuitable for differentiation. To understand the inevitability of the fusion among myoblasts, we prepared heterokaryons in crosses between quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells) and rodent non-myogenic cells, such as tumor cells, fibroblasts, or neurogenic cells by HVJ (Sendai virus) and examined how myogenic differentiation was influenced in the prepared heterokaryons, focusing on myogenin expression and myofibril formation as markers of differentiation. When presumptive QM-RSV cells were fused with non-myogenic cells by HVJ and induced to differentiate, both myogenin expression and myofibril formation were suppressed. When myotubes of QM-RSV cells that had already expressed myogenin and formed myofibrils were fused with non-myogenic cells, both myogenin and myofibrils disappeared. Especially, fibrous structures of myofibrils were significantly lost and dots or aggregations of F-actin were formed within 24 hr after formation of heterokaryons. However, the fusion of presumptive or differentiated QM-RSV cells with rodent myoblasts did not disturb myogenin expression or myofibril formation. These results suggest that mutual fusion of myoblasts is indispensable for normal myogenic differentiation irrespective of the species, and that some factors inhibiting myogenic differentiation exist in the cytoplasm of non-myogenic cells, but not in myoblasts.

Animals↗

PubMed2001

[Anesthesia for electroconvulsive therapy during pregnancy--a case report].

We experienced anesthetic management for ECT in a patient with psychiatric disease during the third trimester of pregnancy. The 24 year-old patient had been on oral antipsychotics prescribed to treat schizophrenia for ten years. Her signs and symptoms deteiorated during pregnancy in spite of increased doses of antipsychotics. With tocolytic agent administered intravenously, anesthesia was induced by intravenous thiamylal immediately followed by intravenous suxamethonium for muscle relaxation. Alternative current was applied on both side of the head after the sufficient anesthesia had been obtained. The patient received intermittent mandatory ventilation by breathing mask with 100% oxygen during the procedure. Along with monitoring of maternal hemodynamic variables and arterial oxygen saturation (Spo2), fetal heart rate and uterine contraction were recorded by cardiotocogram throughout the procedure. At the first two treatments, the patient showed neither significant uterine contraction nor fetal heart rate changes. At the third treatment, continuous uterine contraction refractory to tocolysis was recorded for six minutes, resulting in fetal bradycardia. At the sixth treatment, general anesthesia was induced and maintained by sevoflurane in oxygen followed by suxamethonium for muscle relaxation. The uterine contraction was remarkably diminished and fetal heart rate remained unchanged during the procedure. In conclusion, inhalation anesthesia is beneficial for ECT in the last stage of pregnancy to reduce uterine contraction by potential uterine relaxation effect of anesthetics.

Adult↗

PubMed2000

Visual and colorimetric lithium ion sensing based on digital color analysis.

A new optical analytical method, "Digital Color Analysis (DCA)", is proposed based on a digital color analyzer instead of the conventional optical methodology, "Spectrophotometry". The digital color analyzer is a hand-held-size instrument for measuring "colors", and it can transform the color information into numerical values, color library data, etc., that can be treated as analytical information. DCA gives us a more informative analytical method than spectrophotometry by treating colors as digital information. In addition, DCA can also simulate the optimum color variations for optimization of the visual sensor with computer assistance. By utilizing colors as digital information, colorimetric analysis that has been used for only semiquantitative analysis can serve as an accurate determination method. On the basis of DCA, we developed a plasticized PVC film optode and a paper optode for Li+ determination in saliva. After the optimization of color variation and the detection range for the Li+ measurements, the optode membrane gives colorless gray in the Li+ therapeutic range (at 10(-3) M) in saliva. Consequently, whether or not the optimum therapeutic Li+ concentration is maintained can be easily evaluated with these optodes. Especially, the sensing paper optode can be easily handled within a short measurement time (approximately 80 s) which is suitable for home use. Using the digital color analyzer with QxQy coordinates, a linear relation calibration curve can be obtained over the range from 10(-5) to 10(-1) M Li+, in which the analyzer can detect a concentration difference of approximately 0.1 mM Li+. For the near future, an accurate and simple analysis is needed for a health check at home that does not require going to a hospital. The optode based on DCA has great potential for this analytical purpose.

Analog-Digital Conversion↗

PubMed2000

Dynamic distribution of an antigen involved in the differentiation of avian myoblasts: II. Possible association of beta1 integrin with myofibril organization.

Previous studies have shown that a monoclonal antibody, H-145, inhibits myotube formation of quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells) [Hyodo and Kim, 1994: Exp. Cell Res. 212:120-131]. The antigen recognized by H-145 (H-145 antigen), which is a glycoprotein with a molecular mass of about 116 kDa, is related to a step immediately before myoblast fusion. To determine the functional significance of H-145 antigen, we examined its dynamic state during myogenic differentiation of QM-RSV cells. H-145 antigen showed a unique and discrete distribution. In immature myotubes immediately after myoblast fusion, many ring-like structures of H-145 antigen appeared on the ventral surface of the cells, encircling the actin dots detected simultaneously by immunofluorescence and interference reflection microscopy. The core of the ring-like structures was filled with the termini of actin bundles, mainly formed by alpha-actin. Other cytoskeletal-associated proteins, such as vinculin and alpha-actinin, were also associated with these structures. The ring-like structures of H-145 antigen were observed only during a restricted period when myoblasts fused actively, suggesting their relationships to myotube formation and an early stage of myofibril formation. With maturation of the myotubes, most of the H-145 antigen became redistributed in linear arrays on the apical cell surface and was probably associated with the termini of actin bundles to organize myofibrils, suggesting that the antigen was also related to maturation of myotubes. Experiments using monoclonal antibodies against chick beta1 integrin showed that H-145 antigen is beta1 integrin or a very closely related derivation. Thus H-145 antigen (beta1 integrin) is possibly involved in both myoblast fusion and the myofibril organization in myotubes.

Actins↗

PubMed2000

Antiviral substance from silkworm faeces: characterization of its antiviral activity.

The antiviral activity of a substance (L4-1) purified from silkworm faeces was examined in an HVJ (Sendai virus)-LLC-MK2 cell system. Its antiviral effect depended on the period of light irradiation and was inhibited by sodium sulfite and anaerobic conditions. These results indicate that the antiviral activity of L4-1 is associated with active oxygen species produced from the substance. SDS-polyacrylamide gel electrophoretic analysis showed that viral proteins were damaged by this substance under light irradiation. The results suggest that the antiviral activity is due to damage to viral protein(s) caused by active oxygen species produced from L4-1.

Animals↗

PubMed1999

Changes in uterine size after vaginal delivery and cesarean section determined by vaginal sonography in the puerperium.

There have been few reports on postpartum changes in the uterus during the three months after delivery. The aim of this study was to evaluate uterine morphological changes in women after vaginal delivery (n=262-351) and in women after cesarean section (n=64-82) and to evaluate the relation between breast-feeding and parity, and uterine involution at 1 and 3 months postpartum measured by vaginal ultrasonography. There were no significant differences in parity between the vaginal delivery group and the cesarean section group. The length of the uterus at one month (7.93+/-1.16 cm, mean+/-SD) and, three months (7.03+/-1.19 cm) and the width of the uterus at three months (3.83+/-0.94 cm) after delivery in the cesarean section group were greater than in the transvaginal group (7.64+/-1.03 cm, 6.65+/-0.99 cm, 3.57+/-0.62 cm, respectively). Increasing maternal parity was associated slightly with larger uterine size at one month post partum. The length of the uterus of women with a breast-feeding rate of 80% or more per day was 6.35+/-0.85 cm, and shorter than in women with a rate of 20% or less 7.03+/-1.04 cm, at three months after delivery. The width of the uterine body of women with a breast-feeding rate of 80% or more per day was 3.32+/-0.45 cm, and shorter than in women with a rate of 20% or less 3.87+/-0.66 cm, at 3 months after delivery. Stepwise regression and multiple regression analysis among parity, the history of cesarean section, the breast-feeding rate at one and three months after the delivery, and the restoration of the menses at three months after the delivery showed that the uterine size at one month after the delivery was related to the cesarean section and that the uterine size at three months after delivery was mostly related to the rate of breast-feeding. These results indicated that uterine involution was related to delivery mode at one and three months postpartum, feeding mode at three months postpartum, the menses restoration, and parity. The rate of breastfeeding was mostly related to the uterine size at three months postpartum.

Adult↗

PubMed1999

Parvovirus B19 infection induces apoptosis of erythroid cells in vitro and in vivo.

OBJECTIVE: intrauterine parvovirus B19 infection is related to non-immune hydrops fetalis, the pathogenesis of which is based on the strict tropism of B19 for erythroid precursor cells and the massive destruction of the infected erythroid cells, although the mechanism of beta19-induced cytotoxicity has not been studied in detail. The purpose of this study is to provide empirical evidence that beta19 induces apoptosis of erythroid cells both in vitro and ill vivo. METHODS: we analysed culture cells infected in vitro by B19 and tissues of nine cases of hydrops fetalis caused by B19 intrauterine infection by histological and biological methods. RESULTS: cells infected iil vitro by B19 showed nuclear changes characteristic of apoptosis by light microscopic examination and DNA extracted from the infected cells was fragmented. Electron microscopic examination showed the nuclei of infected cells contained crescent-shaped clumps of heterochromatin with increased density and double staining with anti-B1 9 antibody and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) confirmed apoptosis of individual cells. Tissues of cases of hydrops fetalis caused by B19 contained erythroid cells with nuclear inclusions and characteristic nuclear changes of apoptosis by light microscopy. The double-staining confirmed apoptosis of erythroid cells in the tissues. Immunohistochemical analysis with antibodies against cellular factors involved in apoptosis showed that caspase3, p53 and p21 were positive in infected cells.

Apoptosis↗

PubMed1999

Mouse C2 myoblast cells resist HVJ (Sendai virus)-mediated cell fusion in the proliferating stage but become capable of fusion after differentiation.

To investigate the mechanism of myoblast fusion, we attempted to prepare artificial myotubes of mouse C2 myoblast cells using the hemagglutinating virus of Japan (HVJ, Sendai virus). Proliferating C2 cells showed strong resistance to HVJ-mediated cell fusion and remained morphologically unchanged even though massive numbers of virions adsorbed onto their surface. They showed no membrane disruption, which occurs in the early stage of cell fusion induced by HVJ. These observations suggest that proliferating C2 cells are resistant to HVJ-mediated cell fusion. However, upon induction of differentiation, C2 cells gradually became capable of fusion induced by HVJ and then even generated heterokaryons with Ehrlich ascites tumor cells. When differentiated C2 cells that had become fusion-sensitive were treated with HVJ in the presence of EDTA, they did not fuse but degenerated, suggesting that their cell membranes were transiently disrupted by interaction with HVJ. These results suggest that the cell membranes of myoblasts change to a fusion-capable state during the process of differentiation.

Animals↗

PubMed1998

Biological activities of a novel lectin derived from silkworm faeces: characteristic changes of mouse peritoneal macrophages by the lectin.

A novel lectin derived from silkworm faeces, named NUE, activates phagocytosis of mouse peritoneal macrophages. At this time, significant morphological changes of the cells take place. NUE-treated macrophages formed projection-like neurocytes within 12 hr of treatment, and appeared somewhat flat in shape with the activation of cell growth. Associated with the morphological changes, actin was organized in dot-like structures corresponding to cell-substratum contact sites in NUE-treated macrophages. Vinculin, a cytoskeletal protein involved in microfilament-membrane interaction, formed doughnut-like rings matching the actin-dots, called "podosomes". Furthermore, observation by interference reflection microscopy showed that NUE-treated macrophages adhered more strongly to the substratum at local areas. According to these changes, more proteins associated with cell-substratum contact sites became to detergent-resistant. It was shown that NUE changed adhesive form of mouse peritoneal macrophages structurally and qualitatively.

Animals↗

PubMed1998

Characterization of myogenin expression in myotubes derived from quail myoblasts transformed with a temperature sensitive mutant of Rous sarcoma virus.

During myogenic differentiation of quail myoblasts transformed with a temperature sensitive mutant of Rous sarcoma virus (QM-RSV cells), it was observed that myogenin was continuously expressed in myotubes. In contrast, in myotubes derived from quail primary cells (parent cells of QM-RSV cells), myogenin expression was seen only in the myotubes not having striated structures comprised of myofibrils, but not in myotubes having the structures. The fact that there are not striated structures of myofibrils formed in myotubes derived from QM-RSV cells suggests that these myotubes stop at an immature state prior to the final differentiation. These results also suggest that myogenin is not only required for early steps during differentiation but also maturation steps of myotubes. To clarify the roles of myogenin after myotube formation and maturation, myotubes derived from QM-RSV cells were treated with N,N'-hexamethylene bisacetamide (HMBA) or incubated at 35.5 degrees C, a permissive temperature of RSV for suppression of myogenin expression. On treatment with HMBA, myogenin expression disappeared and myotubes began to incorporate 5-bromo-2'-deoxyuridine (BrdU) into the nuclei, whereas the expression remained in many myotubes on culture at 35.5 degrees C. These results suggest that immature myotubes can return to an up step of differentiation, prior to the commitment step with HMBA treatment, but not with culture at 35.5 degrees C.

Acetamides↗

PubMed1997

Myogenin expression is necessary for commitment to differentiation and is closely related to src tyrosine kinase activity in quail myoblasts transformed with Rous sarcoma virus.

Quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells) proliferate at 35.5 degrees C, a permissive temperature for RSV, but differentiate at 41 degrees C, a nonpermissive temperature, with the formation of multinucleated myotubes and the synthesis of muscle-specific proteins. Tyrosine kinase activity of the src gene product derived from RSV is closely related to regulation of this temperature-dependent differentiation, and the cells obtain commitment to differentiation by incubation for about 12 h at 41 degrees C with dephosphorylation of tyrosine-phosphorylated protein(s). It was examined how myogenin, a member of myogenic regulatory factors, participates in commitment to differentiation and tyrosine dephosphorylation of QM-RSV cells. Myogenin was expressed within 8 h and reached a plateau within 10 h at 41 degrees C. Each cell clone whose differentiation proceeded faster or slower than the parental QM-RSV cells was reflected by a faster or slower myogenin expression, corresponding to the time that is required for commitment to differentiation. It was suggested that there is a lag time between myogenin expression and the acquisition of commitment in QM-RSV cells. On the other hand, at 35.5 degrees C, a condition which suppresses differentiation, myogenin expression was not detected. However, herbimycin A, an inhibitor of protein tyrosine kinase, induced myogenin expression even at 35.5 degrees C. On the contrary, myogenin expression was inhibited at 41 degrees C by sodium orthovanadate, an inhibitor of tyrosine-phosphorylated protein phosphatase. Furthermore, forced induction of myogenin into the cells cultured at 35.5 degrees C resulted in the formation of multinucleated myotubes and the synthesis of muscle-specific proteins. These results suggest that myogenin expression is one of the indispensable conditions for the acquisition of commitment to differentiation and is regulated by tyrosine phosphorylation and dephosphorylation of some protein(s) in QM-RSV cells.

Animals↗

PubMed1996

Further investigation of some inhibitors on myogenic differentiation: mechanism of inhibition with HMBA on quail myoblasts transformed with Rous sarcoma virus.

To investigate the mechanism of myogenic differentiation, we are using quail myoblast cells (QM cells) transformed with a temperature-sensitive mutant of Rous sarcoma virus (ts-RSV), termed QM-RSV cells. At 35.5 degrees C, a permissive temperature for RSV, QM-RSV cells repeatedly proliferate without differentiation, but, at 41 degrees C, a nonpermissive temperature, myogenic differentiation proceeds. This temperature dependency of the differentiation is derived from protein kinase activity of pp60v-src, as tyrosine dephosphorylation is necessary for myogenic differentiation of QM-RSV cells. In this study, it was demonstrated that among four fusion inhibitors, aspirin, doxorubicin, HMBA and TPA, three of the inhibitors, except for TPA, inhibited myogenin gene expression. Moreover, HMBA inhibited myoblast fusion accompanying inhibition of tyrosine dephosphorylation of certain proteins, and recovered the tyrosine kinase activity of pp60v-src to a certain extent. To study the effect of HMBA on the intracellular localization of pp60v-src, detergent-soluble and detergent-resistant fractions were prepared with Triton X-100. As a result, it was shown that pp60v-src mainly exists in detergent-resistant fraction at 35.5 degrees C. While almost all of the pp60v-src at 41 degrees C exists in detergent-soluble fraction. HMBA treatment retained pp60v-src in detergent-resistant fraction even at 41 degrees C. These results suggest that HMBA inhibits myogenic differentiation of QM-RSV cells by affecting the regulation of pp60v-src.

Acetamides↗

PubMed1995

Effects of some inhibitors on myogenic differentiation of avian myoblasts transformed with Rous sarcoma virus.

The differentiation of quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma virus (QM-RSV cells) depends on culture temperature. At 35.5 degrees C, the permissive temperature for RSV, QM-RSV cells repeatedly proliferate without differentiation. However, myogenic differentiation proceeds at 41 degrees C, the nonpermissive temperature for RSV. To obtain useful inhibitors for the analysis of myogenic differentiation in QM-RSV cells, various drugs of myoblast fusion reported previously were examined in the QM-RSV system. Thirteen of twenty-seven drugs tested blocked myoblast fusion of QM-RSV cells. Among inhibitors that blocked the fusion of QM-RSV cells, four of them, acetylsalicylic acid (aspirin), 12-o-tetradecanoyl phorbol-13-acetate (TPA), doxorubicin, and N,N'-hexamethylenebisacetamide (HMBA), were chosen for further analysis. Two parameters of myogenic differentiation, myotube formation by myoblast fusion and creatine kinase activity, were examined. Aspirin, doxorubicin, and HMBA, inhibited myoblast fusion by acting on both steps before and after commitment for myoblast fusion. TPA affected the step before commitment for fusion. The effects of these inhibitors on creatine kinase activity were not always in parallel with myoblast fusion, suggesting that the process of myoblast fusion and the expression of creatine kinase activity are separate phenomena. Aspirin and doxorubicin did not affect creatine kinase activity. On the contrary, doxorubicin accelerated creatine kinase activity about twofold when the cells were treated with this drug after commitment in spite of strong inhibition of myoblast fusion. The expression of Mb-N3 and H145 antigens, which are closely related to the differentiation of QM-RSV cells, was affected variously by these inhibitors and sodium orthovanadate, an inhibitor of protein-phosphotyrosine phosphatase, suggesting that these inhibitors act on different steps during differentiation.

Animals↗

PubMed1995

The effects of bifemelane hydrochloride on depressive illness of the elderly.

The therapeutic efficacy, utility and safety of bifemelane hydrochloride were studied in 52 elderly depressive patients. The drug was administered as a tablet containing 50 mg orally three times daily for 8 consecutive weeks. The final global improvement rating and global utility rating were respectively 80.8 and 73.1 percent for all patients. The improvement rates on the Hamilton depression rating scale (HAM-D) were more than 60% for depressed mood, guilt, suicide, middle insomnia, delayed insomnia, psychotic anxiety, gastro-intestinal symptom, hypochondriasis, depersonalization and derealization. The rates regarding global symptoms evaluated by the Psychoneurotic rating scale for doctor's use were more than 60% for tension, agitation, irritability and excitement, phobia, depression, hypochondria and nocturnal delirium in psychotic symptoms, and insomnia in addition to palpitation in somatic symptoms. A significant decrease was also observed in the symptoms covered by the Self-rating depression scale of Zung after treatment with this drug. There were no instances of side-effects, nor any abnormalities in laboratory tests, encountered throughout the trial. Therefore, bifemelane hydrochloride is of value for the treatment of geriatric depression.

Aged↗