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OBJECTIVE: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. METHODS: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms "thrombocytopenia" and "platelet count decreased") occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. RESULTS: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56-1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6-26.7) months. CONCLUSION: Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759587.
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OBJECTIVE: Epithelial ovarian cancer (EOC) is the leading cause of female mortality in gynecologic malignancies, with a rising incidence in Japan. This study aimed to validate the treatment patterns and safety of niraparib as maintenance therapy for EOC following initial chemotherapy in clinical practice in Japan. METHODS: Leveraging claims data between April 2008 and December 2022, this descriptive study comprised EOC-diagnosed patients receiving initial platinum-based chemotherapy, debulking surgery, and niraparib as maintenance therapy. Patient characteristics, prescription status, transfusion details, and laboratory data were assessed and reported as summary statistics and frequencies. RESULTS: Among 291 patients, the median age was 64.0 years and 94.5% received a 200-mg daily dose of niraparib. At week 12, 78.7% (229/291) continued niraparib treatment, 21.3% (62/291) discontinued, and 52.2% (152/291) required treatment interruptions. Of the 62 patients who discontinued treatment, 27 patients initiated subsequent EOC treatment within 12 weeks following niraparib discontinuation. Blood transfusions were needed in 10.3% (30/291), and of 55 patients with available laboratory data, 61.8% (34/55) had decreased platelet count <100,000/µL, 25.5% (14/55) had decreased hemoglobin level <8 g/dL, and 22.7% (5/22) had decreased neutrophil count <1,000/µL, meeting the criteria for treatment interruption. Among those with thrombocytopenia, 88.2% (30/34) were able to either resume or continue treatment. CONCLUSION: Niraparib demonstrated favorable tolerability in Japanese patients with advanced EOC, with effective management of thrombocytopenia through dose adjustments and supportive care, supporting its viability as post-chemotherapy maintenance therapy.
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Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7-7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2-37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7-2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6-13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8-5.1]; dual-agent: 12.4% [95% CI 8.0-16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4-35.2]; dual-agent: 44.3% [95% CI 31.7-56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0-12.2]; dual-agent: 16.3 months [95% CI 13.5-19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.
Subject(s)
Immune Checkpoint Inhibitors , Melanoma , Uveal Neoplasms , Uveal Neoplasms/drug therapy , Uveal Neoplasms/mortality , Uveal Neoplasms/pathology , Melanoma/drug therapy , Melanoma/mortality , Melanoma/pathology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Neoplasm Metastasis , Treatment Outcome , Progression-Free SurvivalABSTRACT
Peritonitis is one of the most important complications in patients with peritoneal dialysis (PD). Appropriate antibiotic treatment against PD-associated peritonitis is necessary to prevent PD catheter removal and withdrawal from PD. Chryseobacterium indologenes is a Gram-negative rod that occurs in the natural environment. C. indologenes is thought to acquire resistance to ß-lactam drugs through the production of metallo-ß-lactamase and to become resistant to antibiotic therapy through the formation of biofilms. Only a few cases of PD-associated peritonitis caused by C. indologenes have been reported to date, and appropriate treatment strategies have not been clarified. In the past, 5 cases of PD-associated peritonitis caused by C. indologenes have been reported and 2 patients required catheter removal because of recurrence or refractoriness. In this case, a 51-year-old man with PD-associated peritonitis caused by C. indologenes was treated with 2 susceptible antibiotics, including fluoroquinolones to prevent acquired resistance and biofilm formation. There was no recurrence, and catheter removal was not necessary in this case. Collectively, the present case highlighted that PD-associated peritonitis caused by C. indologenes should be treated with 2 susceptible antibiotics including fluoroquinolones for 3 weeks.
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Teleost fishes exhibit complex sexual characteristics in response to androgens, such as fin enlargement and courtship display. However, the molecular mechanisms underlying their evolutionary acquisition remain largely unknown. To address this question, we analyse medaka (Oryzias latipes) mutants deficient in teleost-specific androgen receptor ohnologs (ara and arb). We discovered that neither ar ohnolog was required for spermatogenesis, whilst they appear to be functionally redundant for the courtship display in males. However, both were required for reproductive success: ara for tooth enlargement and the reproductive behaviour eliciting female receptivity, arb for male-specific fin morphogenesis and sexual motivation. We further showed that differences between the two ar ohnologs in their transcription, cellular localisation of their encoded proteins, and their downstream genetic programmes could be responsible for the phenotypic diversity between the ara and arb mutants. These findings suggest that the ar ohnologs have diverged in two ways: first, through the loss of their roles in spermatogenesis and second, through gene duplication followed by functional differentiation that has likely resolved the pleiotropic roles derived from their ancestral gene. Thus, our results provide insights into how genome duplication impacts the massive diversification of sexual characteristics in the teleost lineage.
Subject(s)
Oryzias , Receptors, Androgen , Animals , Male , Female , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Fishes/genetics , Fishes/metabolism , Biological Evolution , Evolution, Molecular , Oryzias/genetics , Oryzias/metabolismABSTRACT
BACKGROUND: Although severe atherosclerotic renal artery stenosis (ARAS) is a predictor of future cardiovascular events, large trials have not shown the benefits of percutaneous transluminal renal angioplasty (PTRA). This study aimed to validate the safety and efficacy of PTRA using low-concentration digital subtraction angiography (LC-DSA) in patients with severe ARAS and advanced chronic kidney disease (CKD). MATERIALS AND METHODS: This prospective study was conducted between August 2018 and October 2021. Eighteen patients with 20 lesions, CKD stage 3b or worse, and significant renal artery stenosis were included and underwent PTRA using ultra-low-dose contrast medium. The primary endpoint was a change in renal function based on serum creatinine (sCr) level. RESULTS: The mean sCr level significantly improved from 3.34 ± 1.8 mg/dL pre-PTRA to 2.48 ± 1.19 mg/dL at 1 month post-PTRA (P = .02). The mean amount of contrast used was 8.3 ± 3.9 mL per vessel. More severe stenosis and rapid deterioration of renal function before treatment were associated with improved kidney function. No cardiovascular or renal complications such as stroke or contrast-induced nephropathy were observed during the 30-day period. CONCLUSIONS: PTRA using an ultra-low-dose contrast medium is safe and provides acceptable results.
Subject(s)
Angioplasty, Balloon , Renal Artery Obstruction , Renal Insufficiency, Chronic , Humans , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/etiology , Renal Artery Obstruction/therapy , Prospective Studies , Treatment Outcome , Kidney/physiology , Angioplasty/adverse effects , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/therapy , Angioplasty, Balloon/adverse effectsABSTRACT
Five cases of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis-associated rapidly progressive interstitial lung diseases (anti-MDA5-positive DM-RPILD) following COVID-19 vaccination have been reported previously. We present the first case of the disease that developed following the sequence of COVID-19 infection, COVID-19 vaccination, and 23-valent pneumococcal polysaccharide vaccine (PPSV23) administration. A 75-year-old-Japanese man received the third dose of Pfizer COVID-19 vaccine 4 weeks after he had a mild COVID-19 infection. Eleven weeks after vaccination, he received PPSV23 for the first time. He developed fever, malaise, and anorexia the day after the PPSV23, rash a week later, and shortness of breath 2 weeks later. He was then admitted to a local hospital and treated with antibiotics, but his condition worsened. He was transferred to our hospital 4 weeks after the PPSV23 and was diagnosed with anti-MDA5-positive DM-RPILD. Despite intensive treatment, the patient died on the 10th hospital day.
ABSTRACT
To reveal optimal antibiotic prophylactic regimen for postoperative endophthalmitis (POE), we conducted systematic review and network meta-analysis. A total of 51 eligible original articles, including two randomized controlled trials, were identified. In total, 4502 POE cases occurred in 6,809,732 eyes (0.066%). Intracameral injection of vancomycin had the best preventive effect (odds ratio [OR] 0.03, 99.6% confidence interval [CI] 0.00-0.53, corrected P-value = 0.006, P-score = 0.945) followed by intracameral injection of cefazoline (OR 0.09, 99.6% CI 0.02-0.42, corrected P-value < 0.001, P-score = 0.821), cefuroxime (OR 0.18, 99.6% CI 0.09-0.35, corrected P-value < 0.001, P-score = 0.660), and moxifloxacin (OR 0.36, 99.6% CI 0.16-0.79, corrected P-value = 0.003, P-score = 0.455). While one randomized controlled trial supported each of intracameral cefuroxime and moxifloxacin, no randomized controlled trial evaluated vancomycin and cefazoline. Sensitivity analysis focusing on the administration route revealed that only intracameral injection (OR 0.19, 99.4% CI 0.12-0.30, corrected P-value < 0.001, P-score = 0.726) significantly decreased the risk of postoperative endophthalmitis. In conclusion, intracameral injection of either vancomycin, cefazoline, cefuroxime, or moxifloxacin prevented POE.
Subject(s)
Cataract Extraction , Endophthalmitis , Humans , Cefuroxime/therapeutic use , Vancomycin , Moxifloxacin/therapeutic use , Antibiotic Prophylaxis , Network Meta-Analysis , Cataract Extraction/adverse effects , Anti-Bacterial Agents/therapeutic use , Endophthalmitis/drug therapy , Endophthalmitis/etiology , Endophthalmitis/prevention & control , Anterior Chamber , Postoperative Complications/prevention & control , Postoperative Complications/drug therapyABSTRACT
BACKGROUND: Ceftazidime encephalopathy is reported to be caused by the repeated administration of ceftazidime in patients with renal impairment because of the high serum concentration of ceftazidime. Ceftazidime encephalopathy has been considered to be caused by the elevation of the cerebrospinal fluid (CSF) concentration. However, as no reports have measured CSF concentrations, the relationship with ceftazidime encephalopathy and CSF concentration has not been clarified. CASE PRESENTATION: Case 1: An 80-year-old Japanese man under a combination therapy with peritoneal dialysis and hemodialysis, who had been treated for a cellulitis with ceftazidime, developed altered consciousness and was diagnosed as ceftazidime encephalopathy. His serum concentration of ceftazidime was elevated, but CSF concentration was only under 0.1 µg/mL. Case 2: An 88-year-old Japanese man with chronic kidney disease, who had been treated for a urinary tract infection with ceftazidime, developed altered consciousness and was diagnosed as ceftazidime encephalopathy. His serum concentration of ceftazidime was elevated, but CSF concentration was within the therapeutic range. However, his serum and CSF concentration of quinolinic acid was markedly increased. CONCLUSIONS: Patients with renal failure are more likely to develop ceftazidime encephalopathy. We need to pay attention to the dosage of ceftazidime and to the appearance of neurological symptoms. Ceftazidime encephalopathy was considered to be caused by the high CSF concentration, but it could be caused by quinolinic acid as neurotoxic substance.
Subject(s)
Brain Diseases , Peritoneal Dialysis , Renal Insufficiency , Aged, 80 and over , Ceftazidime/adverse effects , Humans , Male , Quinolinic AcidABSTRACT
A 70-year-old woman, who started on hemodialysis 7 months before for end-stage renal disease due to diabetic nephropathy and was diagnosed with symptomatic multiple myeloma 1 month before, was admitted to our hospital with critical coronavirus disease 2019 and treated with long-term immunosuppressive therapy such as steroids and tocilizumab. During treatment, Bacillus subtilis was detected in the blood cultures. We could not exclude the association of natto (fermented soybeans) with B. subtilis var. natto, which the patient had been eating every day from 8 days after admission. She was prohibited from eating natto and treated with vancomycin. Later, B. subtilis detected in the blood culture was identified as B. subtilis var. natto, which was identical with those contained in the natto that the patient consumed daily using a next-generation sequencer. Gut dysbiosis due to old age, malignant tumor, diabetes mellitus, end-stage renal disease, and intestinal inflammation caused by severe acute respiratory syndrome coronavirus 2 increased intestinal permeability and the risk of bacterial translocation, causing B. subtilis var. natto bacteremia. Therefore, careful consideration might be given to the intake of fermented foods containing live bacteria in patients with severe immunocompromised conditions.
Subject(s)
Bacteremia , COVID-19 Drug Treatment , COVID-19 , Kidney Failure, Chronic , Multiple Myeloma , Soy Foods , Aged , Bacillus subtilis , Bacteremia/drug therapy , COVID-19/complications , Eating , Female , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Renal Dialysis , Soy Foods/microbiologyABSTRACT
Background: We experienced that some hemodialysis (HD) patients with coronavirus disease 2019 (COVID-19) exacerbated hypoxemia during HD. Though HD-induced hypoxemia has been reported, there have been no reports of HD-induced hypoxemia in patients with COVID-19 and its effect on prognosis of COVID-19. Methods: Eleven HD patients admitted with COVID-19 from August 2020 to April 2021 were classified into the patients whose oxygen demand increased by more than 3 L/min with mask during HD (worsened group, n = 5) and others (not-worsened group, n = 6). The background, laboratory findings, severity of COVID-19 and prognosis were compared between the two groups. In addition, blood gases were measured before and after dialysis among HD patients admitted with COVID-19 on April 2021 (n = 3). Results: There were no significant differences in backgrounds, except for a higher proportion of diabetes mellitus in worsened group (p = 0.04). Although laboratory findings were not significantly different on admission day, albumin and LDH levels 7 days after admission were significantly lower and higher in worsened group, respectively (p = 0.03 and < 0.01). The severity of COVID-19 and survival rate were significantly worse in worsened group (p = 0.01 and 0.03). The alveolar-arterial oxygen pressure difference (Aa-DO2) opened during HD in a patient with HD-induced hypoxemia, but did not open in patients without HD-induced hypoxemia. Conclusions: There is a close relationship among HD-induced hypoxemia and poor prognosis of COVID-19. The HD-induced hypoxemia of patients with COVID-19 may be caused by ventilation/perfusion mismatching. Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-022-00408-5.
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BACKGROUND: The mortality rate of Coronavirus disease 2019 (COVID-19) is extremely high in hemodialysis patients (HDP). These patients also develop lower antibody titers after vaccination. Therefore, factors associated with antibody titers and vaccine efficacy in HDP with breakthrough infection need to be investigated. METHODS: We measured anti-S1 antibody titers in HDP (n = 104) and controls (n = 35), evaluating the influence of background on HDP by multivariable regression analysis. We classified 26 HDP patients admitted with COVID-19 into the unvaccinated (n = 15) and breakthrough infection group (n = 11), performing between-group comparisons of laboratory findings and prognosis. Vaccinated COVID-19 patients were classified into HDP and non-HDP controls, and compared the relationship between antibody titer and severity, and the prognosis of breakthrough infection. RESULTS: The antibody titer was significantly lower in the HDP group than in the control group. Among HDP, age and smoking history were significantly independent factors associated with antibody titer. The breakthrough infection group had significantly better laboratory findings (KL-6 and LDH), severity, and hospitalization period than the unvaccinated group even if antibody titers were lower than the known threshold for neutralization (p < 0.05). There was no significant difference in prognosis between the HDP and non-HDP with breakthrough infection. Severity of COVID-19 tended to be higher with lower antibody titer in non-HDP, but not in HDP. CONCLUSION: Vaccines improved the severity of COVID-19 and hospitalization period of breakthrough infection in HDP, although HDP, especially in elderly smokers had lower antibody titers than control. There was no significant association between antibody titer and severity in HDP.
Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , Humans , Prognosis , Renal DialysisABSTRACT
We aimed to assess the clinical utility of BD KiestraTM Urine Culture App (UCA). High concordance rates were observed between the urine culture colony counts obtained by medical technologists and those produced using UCA. This application may increase the efficiency of obtaining semi-quantitative urine culture results.
Subject(s)
Bacteriological Techniques/methods , Urinalysis/methods , Urine/microbiology , AutomationABSTRACT
BACKGROUND: In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature. CASE PRESENTATION: This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018. CONCLUSIONS: Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.
Subject(s)
Panuveitis , Sarcoidosis , Uveitis , Antiviral Agents/adverse effects , Female , Humans , Middle Aged , Panuveitis/chemically induced , Panuveitis/drug therapy , Ribavirin/adverse effects , Sarcoidosis/chemically induced , Sarcoidosis/diagnosis , Sarcoidosis/drug therapy , Uveitis/chemically induced , Uveitis/diagnosisABSTRACT
In Europe and the United States, beginning steroid treatment on the day before docetaxel(DTX)administration is recommended to reduce edema and/or hypersensitivity symptoms. In this study, we investigated the usefulness of starting steroid treatment on the day before DTX administration. Patients with breast cancer who received 4 or more cycles of DTX with or without trastuzumab or DTX and cyclophosphamide(TC)with or without trastuzumab as pre- or post-operative chemotherapy in our hospital between January 2010 and May 2012 were analyzed in this retrospective study. Patients were classified as those who started taking steroids on the day of DTX administration(GroupA: 62 patients)and those who started taking steroids on the day before DTX administration(GroupB: 47 patients). The incidence of edema and/or hypersensitivity was retrospectively compared between these groups after the completion of 4 cycles of chemotherapy. The incidence of edema was significantly lower in GroupB (n=12, 25.5%)than in GroupA (n=28, 45.2%; p=0.04). The onset of edema also tended to be later in GroupB. The incidence of hypersensitivity tended to be lower in GroupB(n=3, 6.4%)than in GroupA (n=8, 12.9%), although this difference was not statistically significant. These results suggest the benefit of steroid treatment started on the day before DTX administration in preventing the development of edema. Results also suggest that the onset of edema could be delayed by this administration method. We recommend that steroid premedication, which can lead to a reduction in adverse drug reactions to DTX, be used to help maintain patients' quality of life(QOL)and to support treatment continuation.
Subject(s)
Breast Neoplasms/drug therapy , Dexamethasone/adverse effects , Edema/prevention & control , Steroids/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Edema/chemically induced , Humans , Middle Aged , Retrospective Studies , Trastuzumab , Treatment OutcomeABSTRACT
We report here a case study of TALEN-induced gene knock out of the trachealess gene of Drosophila. Two pairs of TALEN constructs caused targeted mutation in the germ line of 39% and 17% of injected animals, respectively. In the extreme case 100% of the progeny of TALEN-injected fly was mutated, suggesting that highly efficient biallelic germ line mutagenesis was achieved. The mutagenic efficiency of the TALEN pairs paralleled their activity of single strand annealing (SSA) assay in cultured cells. All mutations were deletion of 1 to 20 base pairs. Merit and demerit of TALEN-based gene knockout approach compared to other genome editing technologies is discussed.
Subject(s)
Drosophila melanogaster/genetics , Endodeoxyribonucleases/metabolism , Gene Knockout Techniques/methods , Animals , Endodeoxyribonucleases/geneticsABSTRACT
BACKGROUND: Cardiac dysfunction is reported in patients with the metabolic syndrome. We assessed the effects of high-phosphorus and zinc-free diet on cardiovascular system in spontaneously hypertensive rats (SHR)/NDmcr-cp (SHR/cp), a rat model of the metabolic syndrome. We also investigated the effects of N-acetyl-L-cysteine (NAC), an antioxidant, on the development of cardiac dysfunction under such conditions. METHODS: Male SHR/cp and control [Wistar Kyoto (WKY)] rats were divided into three groups and fed control diet (P 0.3% w/w, Zn 0.2% w/w) or high-phosphorus and zinc-free (P 1.2% w/w, Zn 0.0% w/w) diet. The latter group was treated with either NAC (1.5 mg/g per day) or vehicle from 6 to 18 weeks of age (n=6 or 8 for each group). RESULTS: High-phosphate and zinc-free diet increased systolic blood pressure in both WKY and SHR/cp. Echocardiography showed that high-phosphate and zinc-free diet markedly reduced left ventricular systolic and diastolic function in SHR/cp. Histopathologically, the same diet induced severe myocardial fibrosis in SHR/cp, and this effect was prevented by NAC. Whereas treatment with NAC prevented diastolic dysfunction induced by the same diet in WKY, it only improved systolic function but not diastolic function in SHR/cp. CONCLUSIONS: High-phosphate and zinc-free diet induced hypertension and cardiac dysfunction. These changes hamper the protective effects of NAC in the metabolic syndrome. SUMMARY: The present study showed that consumption of high-phosphorus and zinc-free diet increased the myocardial expression of connective tissue growth factor and reduced the expression of metallothionein, which enhanced the development of severe cardiac dysfunction in rats with the metabolic syndrome. The results suggest that the metabolic syndrome seems to aggravate cardiac dysfunction and hamper the protective effects of antioxidant, NAC.