Association of social isolation and loneliness with chronic low back pain among older adults: A cross-sectional study from Japan Gerontological Evaluation Study (JAGES).

BACKGROUND: Per the biopsychosocial model, pain, especially chronic low back pain, which often presents with nonspecific pain, requires a comprehensive approach involving social factors. However, the association of social factors, including social isolation and loneliness, with this condition remains unclear. This study examined the cross-sectional association of social isolation and loneliness with chronic low back pain among older adults. METHODS: We recruited functionally independent older adults through a mail survey in 2019 from the Japan Gerontological Evaluation Study (JAGES). Chronic low back pain was defined as low back pain lasting more than three months. Social isolation was identified based on face-to-face and non-face-to-face interactions ("not isolated," "isolated tendency," and "isolated"). Loneliness was assessed using the UCLA Loneliness Scale ("not lonely," "lonely tendency," and "lonely"). RESULTS: Consequently, 21,463 participants were analyzed (mean age: 74.4 years; 51.5% females); 12.6% reported chronic low back pain. Multivariable Poisson regression analysis revealed that loneliness was significantly associated with the likelihood of chronic low back pain; compared with "not lonely", the prevalence ratio (PR) was 1.14 (95% confidence interval [CI]: 1.05-1.25) for "lonely tendency" and 1.40 (1.27-1.54) for "lonely." Social isolation was not associated; compared with "not isolated," the PR (95% CI) was 0.96 (0.88-1.05) for "isolated tendency" and 0.99 (0.89-1.10) for "isolated." A positive multiplicative interaction between social isolation and loneliness for chronic low back pain was found. CONCLUSIONS: Lonelier individuals were more likely to experience chronic low back pain, and those with loneliness and social isolation were synergistically more likely for this condition.

Fatal pulmonary co-infection with pneumocystis and cytomegalovirus in a patient with acquired immunodeficiency syndrome.

A 33-year-old homosexual Japanese man who admitted to having sex with men presented with a two-week history of dyspnea and fever. Chest imaging showed diffuse pulmonary frosted-glass-like shadows. A blood test revealed positive HIV antibodies with a CD4 cell count of 66/µL. Bronchoalveolar lavage identified pneumocystis. Although the patient exhibited a transient response to anti-pneumocystis treatment and mega-dose steroid pulse therapy, he eventually died from respiratory failure. An autopsy suggested massive cytomegalovirus and pneumocystis pneumonitis. The pulmonary co-infection with cytomegalovirus may have been worsened by the use of mega-dose steroids, and such therapy should be avoided in patients with a high HIV viral load and low CD4 count.

Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes.

Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of ß-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

Insufficient ascorbic acid intake during gestation induces abnormal cardiac dilation in fetal and neonatal SMP30/GNL knockout mice.

BACKGROUND: Despite the acknowledged importance of ascorbic acid (AA) in maintaining pregnancy and normal fetal development, its precise actions remain obscure. Therefore, we investigated the impact of maternal AA content on the growth of fetal mice during the gestation period using senescence marker protein-30/gluconolactonase (SMP30/GNL) knockout (KO) mice, which cannot synthesize AA in vivo. METHODS: SMP30/GNL KO mice gave birth after a gestation period under conditions of absent, low, or normal AA intake. AA was measured using high-performance liquid chromatography and electrochemical detection. Whole-body sections were stained with hematoxylin and eosin, Elastica van Gieson, and Azan. RESULTS: The mothers in the group absent AA intake failed to bear young because of incomplete fetal development. Offspring born under the low-AA condition generally died within a few days after birth. Morphological analysis revealed that the latter neonates of SMP30/GNL KO mothers whose intake of AA was low during gestation manifested abnormal cardiac dilation, congestion of the liver and lungs, incompletely expanded pulmonary alveoli, and impaired vertebral bodies. In contrast, a normal AA diet produced healthy progeny. CONCLUSION: A diet sufficiently replete with AA is essential during the gestational period for normal tissue development in the fetus and neonate.

The measurement of axillary moisture for the assessment of dehydration among older patients: a pilot study.

PURPOSE: Dry axilla can sometimes be found among dehydrated older patients. In this study, we measured the axillary moisture and assessed it as possible marker for dehydration. METHODS: Twenty-nine older patients admitted with acute medical conditions participated in this study. Dehydration was diagnosed by the calculated serum osmolality of greater than 295 mOsm/L. The moisture of axilla was measured by a skin moisture impedance meter which was applied at the center of axilla of patients. RESULTS: 11 patients (7 males and 4 females) were diagnosed as dehydrated and 18 patients (10 males and 8 females) were diagnosed as non-dehydrated. The mean axillary moisture (33%) in the dehydrated group was significantly lower than that (42%) in the non-dehydrated group (p<0.05). The axillary moisture ≥50% showed the sensitivity of 88%. The axillary moisture <30% showed the specificity of 91%. Use of a single cutoff value of 40% moisture produced the sensitivity of 59% and the specificity of 9%. As for the physical signs, dry axilla had also moderate sensitivity and excellent specificity to detect dehydration. CONCLUSIONS: The measurement of the axillary moisture could help assess dehydration. Dehydration could be ruled out when the axillary moisture ≥50%, while it could be ruled-in when the axillary moisture is <30%.

Physical signs of dehydration in the elderly.

OBJECTIVE: Dehydration is a common condition and frequent cause of hospitalization in older people, despite the caregiver's high attention in attempt to avoid its occurrence. In this study, various physical signs were examined as clinical signs of dehydration in elderly. METHODS: A prospective observational study was conducted in an acute care teaching hospital. Consecutive elderly patients who were admitted to the Department of Medicine were evaluated. Dehydration was defined as a calculated serum osmolality above 295 mOsm/L. The patients diagnosed as dehydrated or not dehydrated were observed for physical signs of dehydration. Data of blood and urine chemistry analysis were also compared between the two groups. RESULTS: A total of 27 elderly patients admitted with acute medical conditions were included in this study. For the physical signs, dry axilla had moderate sensitivity (44%) and excellent specificity (89%) to detect dehydration. Sunken eyes and delayed capillary refill time also showed relatively good specificity (83%). For laboratory data, the mean concentrations of serum sodium of the dehydrated group (146 mEq/L) was significantly higher (p<0.01) than those of the non-dehydrated group (134 mEq/L). CONCLUSION: Physical signs of dehydration in elderly showed relatively good specificity but poor sensitivity. The evaluation of the axillary moisture could help assess dehydration as well as laboratory data analysis such as serum sodium concentration.

Pathogenicity of Pasteurella pneumotropica in immunodeficient NOD/ShiJic-scid/Jcl and immunocompetent Crlj:CD1 (ICR) mice.

Pasteurella pneumotropica is an opportunistic pathogen in rodents. Natural infection in immunodeficient animals suggests that immunodeficiency is a major factor in P. pneumotropica pathogenesis. To understand this process, we performed clinical, pathological and bacteriological studies of immunodeficient NOD/ShiJic-scid/Jcl and immunocompetent Crlj:CD1 (ICR) mice experimentally infected with P. pneumotropica ATCC 35149. From 14 days postinoculation, some of P. pneumotropica-infected NOD/ShiJic-scid/Jcl mice developed clinical signs of weight loss. Three of 10 P. pneumotropica-infected NOD/ShiJic-scid/Jcl mice developed clinical signs of depression, ruffled coat, and weight loss and died at 27, 34, and 59 days postinoculation. At 35 days postinoculation, almost all P. pneumotropica-infected NOD/ShiJic-scid/Jcl mice had lung abscesses. The bacteria were isolated from the upper and lower respiratory tracts, including the lungs, and blood. In contrast, P. pneumotropica-infected ICR mice exhibited no clinical signs or lesions. The bacteria were isolated from the upper, but not the lower respiratory tracts. We developed an animal model for understanding host interactions with P. pneumotropica.

Adult onset cardiac dilatation in a transgenic mouse line with Galß1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes: a new model for dilated cardiomyopathy.

Sugar chain abnormalities in glycolipids and glycoproteins are associated with various diseases. Here, we report an adult onset cardiac dilatation in a transgenic mouse line with Galß1,3GalNAc α2,3-sialyltransferase II (ST3Gal-II) transgenes. The transgenic hearts at the end-stage, at around 7 months old, were enlarged, with enlarged cavities and thin, low-tensile walls, typical of dilated cardiomyopathy. Although no apparent change was found in heart gangliosides, glycosylation of heart proteins was altered. Interestingly, sugar moieties not directly related to the ST3Gal-II catalytic reaction were also changed. Significant increases in calreticulin and calnexin were observed in hearts of the transgenic mice. These results suggest that expression of ST3Gal-II transgenes induces abnormal protein glycosylation, which disorganizes the endoplasmic/sarcoplasmic reticulum quality control system and elevates the calreticulin/calnexin level, resulting in suppression of cardiac function. The transgenic mice showed 100% incidence of adult onset cardiac dilatation, suggesting great potential as a new model for dilated cardiomyopathy.

Pituitary-adrenal functions in a hereditary hypothyroid (rdw) rat.

The rdw rat is a hereditary hypothyroid strain isolated from Wistar-Imamichi rats. In the present study, adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint stress (120 min) were examined in rdw adult male rats. ACTH response to restraint stress was higher in rdw rats than in hetero control rats. The plasma concentrations of corticosterone were lower in rdw rats than in control rats during the first 30 min after the onset of stress. Both ACTH and corticosterone responses to restraint stress in rdw rats recovered to control levels after thyroxine (T4) replacement therapy. These results suggest that hereditary hypothyroidism causes adrenal dysfunction directly and that hypersecretion of ACTH is a result of reduced corticosterone in rdw rats.

[Usefulness of sharing medication-related reviews based on questionnaire survey, and the cooperation between hospital and community pharmacist at conference prior to discharge].

Owing to the Japanese healthcare system reform, the place where patients receive medical care is beginning to shift from hospital to home. This study aims to evaluate the usefulness of sharing medication-related reviews through a questionnaire survey and hospital pharmacist intervention survey. It appears that almost all community pharmacists have inadequate information at the time of dispensing medication to, monitoring adverse effects of, and counseling cancer patients. There is no doubt that hospital pharmacists should provide more information to community pharmacists at conference prior to discharge. Fortunately, at the Tokyo Women's Medical University Hospital, hospital pharmacists and community pharmacists work closely to contribute to an effective patient care at discharge. Thus, there is an urgent need to ensure greater cooperation between hospital pharmacists and community pharmacists in Japan.

Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

OBJECTIVE: To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. ANIMALS: 24 Beagles. PROCEDURES: 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. RESULTS: After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Dissection and identification of regions required to form pseudoparticles by the interaction between the nucleocapsid (N) and membrane (M) proteins of SARS coronavirus.

When expressed in mammalian cells, the nucleocapsid (N) and membrane (M) proteins of the severe acute respiratory syndrome coronavirus (SARS-CoV) are sufficient to form pseudoparticles. To identify region(s) of the N molecule required for pseudoparticle formation, we performed biochemical analysis of the interaction of N mutants and M in HEK293 cells. Using a peptide library derived from N, we found that amino acids 101-115 constituted a novel binding site for M. We examined the ability of N mutants to interact with M and form pseudoparticles, and our observations indicated that M bound to NDelta(101-115), N1-150, N151-300, and N301-422, but not to N1-150Delta(101-115). However, pseudoparticles were formed when NDelta(101-115) or N301-422, but not N1-150 or N151-300, were expressed with M in HEK293 cells. These results indicated that the minimum portion of N required for the interaction with M and pseudoparticle formation consists of amino acids 301-422.

Anti-tumor effects of water-soluble propolis on a mouse sarcoma cell line in vivo and in vitro.

The honeybee product propolis and its extracts are known to have biological effects such as antibiotic, anti-viral, anti-inflammatory and anti-tumor activities. This study was designed to investigate whether water-soluble propolis (WSP) inhibits tumor growth. The tumor cell line used was mouse sarcoma 180 (S-180), and its growth was determined in vitro and in vivo with exposure to different concentrations of WSP. The effects of WSP on tumor cells in vitro were evaluated by measuring the intracellular uptake of 3H-thymidine. 3H-thymidine uptake was inhibited in accordance with the concentration of WSP. The minimum concentration of WSP necessary for 3H-thymidine uptake inhibition was 1.0 microg/ml and uptake was suppressed to 88% of the level in non-treated cells at this concentration. In an experiment using tumor-bearing mice, oral administration of WSP was begun 24 hours after transplantation of S-180 cells. WSP was administered to the mice 5 times, every other day for 10 days. The doses were 320 mg/kg (10 mg/mouse) or 960 mg/kg (30 mg/mouse) of body weight. All mice were sacrificed 10 days after transplantation, and tumor growth was evaluated. The orally administered WSP significantly inhibited the growth of transplanted tumors (p < 0.05). Furthermore, histological findings revealed a significant reduction in mitotic cells and tumor invasion of the muscular tissue at both dose-levels of WSP.

Theoretical basis for herbal medicines, Tokishakuyaku-San and Sairei-To, in the treatment of recurrent abortion: enhancing the production of granulocyte-macrophage colony-stimulating factor in decidual stromal cells.

PROBLEM: To get insight into the basis for the empirical usage of herbal medicines, such as Tokishakuyaku-san (Toki) and Sairei-to (Sai) in the treatment of recurrent abortion and intrauterine growth restriction, we examined whether these medicines modulate the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine working as an important mediator for intercellular communication in the embryonic development, in decidual stromal cells (DSCs). METHOD OF STUDY: Human DSCs were cultured with either Toki or Sai at several different concentrations. The effect on cell proliferation was assessed by WST-8 assay. GM-CSF released into culture medium was analyzed using enzyme-linked immunosorbent assay, and semi-quantitative polymerase chain reaction was carried out to see GM-CSF mRNA expression in DSCs. RESULTS: Sai inhibited the proliferation of cultured DSCs, while no interference was observed in the presence of Toki. Both Toki and Sai enhanced the release of GM-CSF into culture medium. The amount of GM-CSF mRNA in cultured DSCs was as well increased by either Toki or Sai. CONCLUSION: Considering the significance of GM-CSF in embryonic development, clinical benefit of these herbal medicines in the treatment of recurrent abortion might be based on the shown pharmacological reaction related to GM-CSF.

Effects of methamphetamine on cortisone concentration, NK cell activity and mitogen response of T-lymphocytes in female cynomolgus monkeys.

As a model for studying methamphetamine (MAP) abuse, which has become a social problem in Japan, we investigated the changes in serum cortisone, NK cell activity and mitogenic response of T-lymphocytes after a single injection of MAP (3.0 mg/kg) in female cynomolgus monkeys. Serum cortisol concentration was significantly elevated to 2.66 times pre-injection levels at 6 h post-injection, and the effect was still observed 24 h later. NK cell activity was significantly elevated at 6 h after MAP injection, but at 24 h after injection had dropped markedly to 49.5% of baseline. Mitogen (PHA) response of lymphocytes was elevated when MAP was injected, and this increased level continued up to 24 h. We speculate that the transient increase in NK cell activity followed by a distinct drop, as well as the changes in T-lymphocytes, may be strongly related to the cortisone concentration.

Successful treatment by double filtrate plasmapheresis in a pregnant woman with the rare P blood group and a history of multiple early miscarriages.

Individuals of P type, a rare blood group, have anti-PP(1)P(k) antibody in their serum, which causes spontaneous abortion in the early stages. We report a patient of p type suffering from multiple spontaneous abortions. We also review previously reported cases from published work. A 36-year-old woman (gravida 2, para 0) was referred to our hospital because of habitual abortion. At the third pregnancy, we started double filtration plasmapheresis (DFPP) from 7 weeks 3 days to remove the antibody. We attained rapid decline in the titer and normal fetal growth. Gradual tapering of the DFPP frequency caused neither a rebound of the titer nor growth retardation. During the course, she experienced only one episode of catheter infection as an adverse effect. At 37 weeks 3 days, after 57 DFPP repetitions, a 2496 g girl was delivered by cesarean section. The infant suffered neither from anemia nor from severe jaundice. A review of previous reports indicates that the titer of the pathogenic antibody should be kept as low as possible from the early gestational stage in P-incompatible habitual abortion cases, otherwise the case typically comes to an unfavorable outcome. Plasma exchanges with fresh plasma potentially induce contamination by either known or unknown pathogens. Such risks are reduced using DFPP because the volume of albumin solution that replaces fresh plasma is less than that by plasma exchange. The present case, along with previous reports, shows that DFPP is an effective therapy for treating P-incompatible pregnancy.

[The effects of fluorescent lamp coated with a photocatalyst film on the number of floating microorganisms or smell molecules in a room installed with the lamp].

Fluorescent lamp that is coated with a photocatalyst film, titanium dioxide (TiO2), can catalyze the microorganisms and smell producing molecules that touch the membrane. In this report, we examined the effect of this coated lamp by the number of floating microorganisms or smell molecules in a room installed with this lamp. The number of floating microorganisms was examined independently in different laboratories before and after installing the lamps in an animal facility and a vegetable processing room of a food company. We found that the number of floating microorganisms was significantly reduced after the installation of this coated lamp. To test for smell molecules, acetaldehyde was injected into a closed chamber installed with the coated lamp and the result was compared to a control where a regular fluorescent lamp was used. The acetaldehyde concentration did not change with the regular lamp but was halved after 1h with the photocatalyst coated lamp. To test the effect in real settings, questionnaires were filled out by restroom users in several different places. About 90% of those surveyed answered that there was a reduction of smell after the installation of the photocatalyst coated lamp. We concluded that the installation of this coated fluorescent lamp reduced not only the floating microorganisms but the smell in various practical situations.

Hypoxia does not reduce HLA-G expression on extravillous cytotrophoblasts.

Placental hypoxia following the immature remodeling of spiral arteries by extravillous cytotrophoblasts (CTs) is focused on the pathogenesis of pre-eclampsia. At the same time, the expression of human leukocyte antigen (HLA)-G is decreased at the protein and mRNA levels in the pre-eclamptic placenta. In view of the potential function of HLA-G in immunological tolerance in the feto-maternal interface, we were much concerned to find whether the lowered expression of HLA-G in the pre-eclamptic placenta is a precursor or the result of placental hypoxia. The effect of oxygen on the expression of membrane-bound (mb) and soluble (s) HLA-G was investigated in primary cultures of extravillous CTs. The undifferentiated CTs isolated from the first-trimester placenta were cultured with different concentrations of oxygen (20%, 8% and 2%). The protein expression of mbHLA-G and of sHLA-G was assessed using flow cytometry, and mRNA expression was analyzed using real-time PCR. Expression of mbHLA-G and of sHLA-G protein was intensified with time in culture regardless of the oxygen concentration, and the expression intensities were synchronized between the 20% and the 2% oxygen concentrations at each time point. The mRNA expressions of mbHLA-G1 and sHLA-G1 at 2% oxygen were increased to twice those with 20% oxygen. Our findings demonstrate that no reduction of HLA-G was induced in CTs by short-term exposure to hypoxia, although further study may be required to find the effect of chronic hypoxia.

A novel method of preoperative autologous blood donation with a large volume of plasma for surgery in gynecologic malignancies.

The objective of this study was to establish a novel method of preoperative autologous blood donation (PAD) for surgery of gynecologic malignancies, which requires considerable amounts of plasma relative to the red blood cell component. To collect a double volume of plasma over the amount obtained from whole blood without using an aphaeresis system, we first collected 500 ml of whole blood (2.5 units), and centrifuged it. We gave back the resultant red cell component alone, and retained the plasma component. We further collected an additional 500 ml of whole blood, and centrifuged it. The red cell component (2.5 units) was stored in the refrigerator (as a concentrated red cell, CRC). The resultant plasma together with the plasma collected first (5 units) was frozen and stored in the freezer (fresh frozen plasma, FFP), We repeated this procedure at most three times at intervals of 1 week. Erythropoietin was injected once a week and iron tablets were prescribed. Ninety-nine patients undergoing surgery for a gynecological malignancy were subjected to this method and 86 patients without PAD served as a control. We conducted the procedure for PAD without any noticeable side effects. The amount of actual use of allogeneic CRC and FFP were significantly reduced in the PAD group compared with the control group. In particular, 93.6% of the PAD cases who gave 10 or less units of FFP could go without allogeneic FFP. Postoperative serum albumin levels were higher in the PAD group compared with the control. We have established a novel PAD method which can yield a greater volume of FFP relative to CRC, thus meeting requirements for surgery for gynecological malignancies.

Time course sequences of angiotensin converting enzyme and chymase-like activities during development of right ventricular hypertrophy induced by pulmonary artery constriction in dogs.

ACE and chymase play crucial roles in the establishment of pressure overload-induced cardiac hypertrophy. In the present study, time sequences of ACE and chymase-like activities, and their correlation with hypertrophic changes including free wall thickness and cardiac fibrosis, were elucidated in dogs with constant pressure overload to the right ventricle. Pulmonary artery banding (PAB) was applied so that the diameter of the main pulmonary artery was reduced to 60% of the original size, right ventricular pressure was elevated by about 70%, and pulmonary artery flow was increased by about three times of that in sham operation groups. These increases remained unchanged 15, 60, and 180 days after PAB, suggesting that constant right ventricular pressure overload was obtained, at least during this period. The diameter of the right ventricular myocyte was slightly increased and the percentage of fractional shortening was decreased 15 days after PAB. Right ventricular wall thickness and interstitial collagenous fiber were, however, not different from those of sham-operated dogs, suggesting that this period is a period of adaptation to the overload. Sixty days after PAB, the diameter of the right ventricular myocyte was further increased, and right ventricular wall thickness and interstitial collagenous fiber were also increased. These changes were almost identical even 180 days after PAB. Thus, stable hypertrophy was elicited from 60 through 180 days after PAB. ACE activity was facilitated at the adaptation period to the overload (15 days after PAB), but chymase activity was not facilitated at this period. On the other hand, both ACE and chymase-like activities were unchanged in the earlier phase (60 days after PAB) of stable hypertrophy, but facilitated in the latter phase (180 days after PAB). These findings suggest the pathophysiologic roles of these enzymes may be different over the time course of pressure overload-induced hypertrophy.