The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, ...fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.
Alport syndrome (AS) is a progressive hereditary renal disease that is characterized by sensorineural hearing loss and ocular abnormalities. It is divided into three modes of inheritance, namely, ...X-linked Alport syndrome (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in
COL4A5
, while ADAS and ARAS are caused by those in
COL4A3
/
COL4A4
. Diagnosis is conventionally made pathologically, but recent advances in comprehensive genetic analysis have enabled genetic testing to be performed for the diagnosis of AS as first-line diagnosis. Because of these advances, substantial information about the genetics of AS has been obtained and the genetic background of this disease has been revealed, including genotype–phenotype correlations and mechanisms of onset in some male XLAS cases that lead to milder phenotypes of late-onset end-stage renal disease (ESRD). There is currently no radical therapy for AS and treatment is only performed to delay progression to ESRD using nephron-protective drugs. Angiotensin-converting enzyme inhibitors can remarkably delay the development of ESRD. Recently, some new drugs for this disease have entered clinical trials or been developed in laboratories. In this article, we review the diagnostic strategy, genotype–phenotype correlation, mechanisms of onset of milder phenotypes, and treatment of AS, among others.
Role of Nox2 in diabetic kidney disease You, Young-Hyun; Okada, Shinichi; Ly, San ...
American journal of physiology. Renal physiology,
04/2013, Volume:
304, Issue:
7
Journal Article
Peer reviewed
Open access
NADPH oxidase (Nox) isoforms have been implicated in contributing to diabetic microvascular complications, but the functional role of individual isoforms in diabetic kidney are unclear. Nox2, in ...particular, is highly expressed in phagocytes and may play a key inflammatory role in diabetic kidney disease. To determine the role of Nox2, we evaluated kidney function and pathology in wild-type (WT; C57BL/6) and Nox2 knockout (KO) mice with type 1 diabetes. Diabetes was induced in male Nox2 KO and WT mice with a multiple low-dose streptozotocin protocol. Groups were studied for kidney disease after 8 and 20 wk of diabetes. Hyperglycemia and body weights were similar in WT and Nox2 KO diabetic mice. All functional and structural features of early and later stage diabetic kidney disease (albuminuria, mesangial matrix, tubulointerstitial disease, and gene expression of matrix and transforming growth factor-β) were similar in both diabetic groups compared with their respective nondiabetic groups, except for reduction of macrophage infiltration and monocyte chemoattractant protein-1 in the diabetic Nox2 KO mice. Systolic blood pressure by telemetry was surprisingly increased in Nox2 KO mice; however, the systolic blood pressure was reduced in the diabetic WT and Nox2 KO mice by tail-cuff. Interestingly, diabetic Nox2 KO mice had marked upregulation of renal Nox4 at both the glomerular and cortical levels. The present results demonstrate that lack of Nox2 does not protect against diabetic kidney disease in type 1 diabetes, despite a reduction in macrophage infiltration. The lack of renoprotection may be due to upregulation of renal Nox4.
ABSTRACT Background BNT162b2, an mRNA COVID-19 vaccine, was launched in many countries as an intramuscular vaccination for COVID-19 infection. Few studies have assessed the physical indications of ...pain at the immunization site. This study aimed to characterize pain at the injection site and investigate morphological attributes using ultrasound. Methods Forty-three of 211 healthcare workers who received a second dose of BNT162b2 between February 2021 and March 2021 were enrolled in the study. The mean age of the subjects was 40 years. We evaluated patients' pain at the injection site using the Numerical Rating Pain Scale (NRPS). We also assessed the thickness of the deltoid muscle fascia at the injection site by ultrasound. Bayesian robust correlation was employed to explore the relationship between the pain intensity scores and ultrasound measurements. Results All eligible subjects complained of pain at the injection site. A median pain onset of 8 hours postvaccination and a median peak intensity score of 4 were reported. Onset of relief occurred after 2 days. Ultrasound images demonstrated a 2.5-fold increase in fascia thickness at the injection site without intramuscular echogenicity change in all subjects. A correlation was established between the NRPS score and the non-injection-to-injection-side ratio of fascia thickness at the injection site (rho = 0.66). Conclusion A sore arm was the most prevalent side effect of BNT162b2 vaccination and could be attributed to temporal fasciitis.
Background
De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed ...by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation.
Methods
This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab.
Results
Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy.
Conclusions
Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.
Depression in dementia patients is associated with complications such as decreased activities of daily living and decreased quality of life. Because pharmacotherapeutic treatments for depression in ...dementia patients may have a poor risk–benefit ratio, effective non‐pharmacotherapeutic interventions are favourable. However, the development of effective treatments requires the identification of depression‐associated factors that can be modified by non‐pharmacotherapeutic means in dementia patients. This systematic literature review aimed to identify modifiable factors related to depression and confirm that these factors can be improved by non‐pharmacotherapeutic interventions. We searched PubMed, SpringerLink, the Web of Science, and the Cochrane Library for articles published between June 2007 and June 2017. We included studies that investigated causes of depression in dementia patients and excluded studies with unclear dementia diagnostic criteria or operational definitions. Of 9004 records screened, 6 studies were included. The participants included community‐dwelling individuals and long‐term care facility residents. The severity of dementia varied from mild to severe. After reviewing the studies, we identified five modifiable relevant factors in community‐dwelling individuals: (i) pain; (ii) neuropsychiatric symptoms; (iii) cognitive decline; (iv) social isolation; and (v) quality of life. In long‐term care facility residents, we identified neuropsychiatric symptoms and quality of life as relevant factors. Our results indicated that non‐pharmacological interventions that improve these factors may improve symptoms of depression. A longitudinal study is recommended to clarify the mechanisms underlying depression symptoms and treatment in dementia patients. In addition, further investigation is needed to elucidate the ways in which differing dementia types and severity affect symptoms of depression.
We examined the hearing management status in early childhood and the hearing level of good-side ears at age 3 and older in 65 children who were detected to have unilateral hearing loss at the first ...examination after newborn hearing screening. Of the 65 children, hearing management had been continued until the age of 3 years or older in 42 cases (65%), hearing management had been completed before the age of 3 years due to normalization of hearing bilaterally in 14 cases (22%), and hearing management had been interrupted because the children stopped visiting our center despite the absence of any change in the status of the unilateral hearing loss in 9 cases (14%). The average hearing level at the final visit (average age 63.6±15.7 months) in the children who had received continuous hearing management up to 3 years of age or later was less than 25 dB in 90% (38/42) of cases. There were 4 cases of hearing loss (1 case of mild hearing loss, 1 case of moderate hearing loss, 2 cases of severe hearing loss), of which the three cases with moderate or more severe hearing loss required hearing aids (even though two of the parents were unaware that the hearing loss in their child had changed from unilateral to bilateral). Hearing on the normal side of children with unilateral hearing loss rarely deteriorates in early childhood, but when it does, it is not always easy for parents to notice. Therefore, it was reconfirmed that it is important for the detailed inspection organization to follow-up regularly.
Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been ...studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dL, and the Uur/Ucr and Cur/Ccr were 0.56±0.14% and 45.7±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.
Obesity related kidney disease Mathew, Anna V; Okada, Shinichi; Sharma, Kumar
Current diabetes reviews
7, Issue:
1
Journal Article
Peer reviewed
Obesity is a risk factor for both de novo disease and as a complication of existing chronic kidney disease. Obesity related disease is characterized by albuminuria, glomerulomegaly and secondary ...focal glomerulosclerosis. Traditionally altered renal hemodynamics causing hyperfiltration and upregulated renin angiotensin system have been associated with these changes. Recently identified circulating factors produced by fat stores such as adiponectin, leptin and inflammatory markers have shown to directly affect the cells in the renal glomeruli and cause pathological changes. Weight loss, blockade of the renin angiotensin system and restoration of adipokine levels may be beneficial to ameliorate the progression of obesity related disease.
The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies ...have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine.
To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels.
The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination.
Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response.
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