Association of blood groups/Rh and diabetes mellitus in Karachi city, Pakistan

Abstract The main purpose of this study was to find out a possible association between ABO blood groups or Rh and diabetes mellitus (DM) in the local population of eight (8) different towns of Karachi, Pakistan. For this purpose a survey was carried out in Karachi to have a practical observation of these towns during the period of 9 months from June 2019 to Feb. 2020. Out of eighteen (18) towns of Karachi, samples (N= 584) were collected from only eight (8) Towns of Karachi and gave a code-number to each town. Diabetic group sample was (n1=432) & pre-diabetes sample was (n2 =152). A standard Abbot Company Glucometer for Random Blood Sugar (RBS) and Fasting Blood Sugar (FBS) tests, standard blood anti sera were used for ABO/Rh blood type. Health assessment techniques were performed ethically by taking informed consent from all registered subjects. Finally data was analyzed by SPSS version 20.0. In our current study, the comparison of ABO blood groups frequencies between diabetic and pre-diabetic individuals were carried out. The percentage values of blood Group-B as given as: (32% in DM vs. 31% in pre-diabetics), followed by blood Group-O as: (18% in DM vs. 11% in pre-diabetics). Contrary to Group-B & O, blood Group-A and Group-AB were distribution percentage higher pre-diabetic as compared to DM patients, as given as: Group-A (32% in pre-diabetics vs. 26% in DM) & Group-AB (26% in pre-diabetics vs. 24% in diabetics patients). In addition, percentage distribution of Rh system was also calculated, in which Rh+ve Group was high and more common in DM patients as compared to pre-diabetics; numerically given as: Rh+ve Group (80% in DM vs. 72% in pre-diabetics). Different views and dimensions of the research topic were studied through literature support, some have found no any association and some established a positive association still some were not clear in making a solid conclusion. It is concluded that DM has a positive correlation with ABO blood groups, and people with Group-B have increased susceptibility to DM disease.

Resumo O objetivo principal deste estudo foi descobrir uma possível associação entre grupos sanguíneos ABO ou Rh e diabetes mellitus (DM) na população local de oito (8) diferentes cidades de Karachi, Paquistão. Para tanto, foi realizado um levantamento em Karachi para observação prática dessas cidades durante o período de 9 meses de junho de 2019 a fevereiro de 2020.De dezoito (18) cidades de Karachi, as amostras (N = 584) foram coletadas de apenas oito (8) cidades de Karachi e deram um número-código para cada cidade. A amostra do grupo de diabéticos foi (n1 = 432) e a amostra de pré-diabetes foi (n2 = 152). Um glicômetro padrão da Abbot Company para testes de açúcar no sangue aleatório (RBS) e açúcar no sangue em jejum (FBS), antissoros de sangue padrão foram usados para o tipo de sangue ABO / Rh. As técnicas de avaliação de saúde foram realizadas de forma ética, tomando o consentimento informado de todos os indivíduos registrados. Finalmente, os dados foram analisados pelo SPSS versão 20.0.No presente estudo, foi realizada a comparação das frequências dos grupos sanguíneos ABO entre diabéticos e pré-diabéticos. Os valores percentuais do sangue do Grupo-B são dados como: (32% em DM vs. 31% em pré-diabéticos), seguido pelo sangue do Grupo-O como: (18% em DM vs. 11% em pré-diabéticos). Ao contrário dos Grupos B e O, sangue do Grupo-A e Grupo-AB tiveram distribuição percentual maior de pré-diabéticos em comparação com pacientes com DM, dado como: Grupo-A (32% em pré-diabéticos vs. 26% em DM) e Grupo AB (26% em pré-diabéticos vs. 24% em pacientes diabéticos). Além disso, também foi calculada a distribuição percentual do sistema Rh, no qual o Grupo Rh + ve foi elevado e mais comum em pacientes com DM em comparação aos pré-diabéticos; dados numericamente como: Grupo Rh + ve (80% em DM vs. 72% em pré-diabéticos). Diferentes visões e dimensões do tema de pesquisa foram estudadas com o suporte da literatura, alguns não encontraram nenhuma associação e alguns estabeleceram uma associação positiva, embora alguns não estivessem claros em fazer uma conclusão sólida. Conclui-se que o DM tem correlação positiva com os grupos sanguíneos ABO, e as pessoas com o Grupo B têm maior suscetibilidade à doença DM.

Association of blood groups/Rh and diabetes mellitus in Karachi city, Pakistan / Associação de grupos sanguíneos/Rh e diabetes mellitus na cidade de Karchi, Paquistão

Abstract The main purpose of this study was to find out a possible association between ABO blood groups or Rh and diabetes mellitus (DM) in the local population of eight (8) different towns of Karachi, Pakistan. For this purpose a survey was carried out in Karachi to have a practical observation of these towns during the period of 9 months from June 2019 to Feb. 2020. Out of eighteen (18) towns of Karachi, samples (N= 584) were collected from only eight (8) Towns of Karachi and gave a code-number to each town. Diabetic group sample was (n1=432) & pre-diabetes sample was (n2 =152). A standard Abbot Company Glucometer for Random Blood Sugar (RBS) and Fasting Blood Sugar (FBS) tests, standard blood anti sera were used for ABO/Rh blood type. Health assessment techniques were performed ethically by taking informed consent from all registered subjects. Finally data was analyzed by SPSS version 20.0. In our current study, the comparison of ABO blood groups frequencies between diabetic and pre-diabetic individuals were carried out. The percentage values of blood Group-B as given as: (32% in DM vs. 31% in pre-diabetics), followed by blood Group-O as: (18% in DM vs. 11% in pre-diabetics). Contrary to Group-"B" & "O", blood Group-A and Group-AB were distribution percentage higher pre-diabetic as compared to DM patients, as given as: Group-A (32% in pre-diabetics vs. 26% in DM) & Group-AB (26% in pre-diabetics vs. 24% in diabetic's patients). In addition, percentage distribution of Rh system was also calculated, in which Rh+ve Group was high and more common in DM patients as compared to pre-diabetics; numerically given as: Rh+ve Group (80% in DM vs. 72% in pre-diabetics). Different views and dimensions of the research topic were studied through literature support, some have found no any association and some established a positive association still some were not clear in making a solid conclusion. It is concluded that DM has a positive correlation with ABO blood groups, and people with Group-B have increased susceptibility to DM disease.

Resumo O objetivo principal deste estudo foi descobrir uma possível associação entre grupos sanguíneos ABO ou Rh e diabetes mellitus (DM) na população local de oito (8) diferentes cidades de Karachi, Paquistão. Para tanto, foi realizado um levantamento em Karachi para observação prática dessas cidades durante o período de 9 meses de junho de 2019 a fevereiro de 2020.De dezoito (18) cidades de Karachi, as amostras (N = 584) foram coletadas de apenas oito (8) cidades de Karachi e deram um número-código para cada cidade. A amostra do grupo de diabéticos foi (n1 = 432) e a amostra de pré-diabetes foi (n2 = 152). Um glicômetro padrão da Abbot Company para testes de açúcar no sangue aleatório (RBS) e açúcar no sangue em jejum (FBS), antissoros de sangue padrão foram usados ​​para o tipo de sangue ABO / Rh. As técnicas de avaliação de saúde foram realizadas de forma ética, tomando o consentimento informado de todos os indivíduos registrados. Finalmente, os dados foram analisados ​​pelo SPSS versão 20.0.No presente estudo, foi realizada a comparação das frequências dos grupos sanguíneos ABO entre diabéticos e pré-diabéticos. Os valores percentuais do sangue do Grupo-B são dados como: (32% em DM vs. 31% em pré-diabéticos), seguido pelo sangue do Grupo-O como: (18% em DM vs. 11% em pré-diabéticos). Ao contrário dos Grupos "B" e "O", sangue do Grupo-A e Grupo-AB tiveram distribuição percentual maior de pré-diabéticos em comparação com pacientes com DM, dado como: Grupo-A (32% em pré-diabéticos vs. 26% em DM) e Grupo AB (26% em pré-diabéticos vs. 24% em pacientes diabéticos). Além disso, também foi calculada a distribuição percentual do sistema Rh, no qual o Grupo Rh + ve foi elevado e mais comum em pacientes com DM em comparação aos pré-diabéticos; dados numericamente como: Grupo Rh + ve (80% em DM vs. 72% em pré-diabéticos). Diferentes visões e dimensões do tema de pesquisa foram estudadas com o suporte da literatura, alguns não encontraram nenhuma associação e alguns estabeleceram uma associação positiva, embora alguns não estivessem claros em fazer uma conclusão sólida. Conclui-se que o DM tem correlação positiva com os grupos sanguíneos ABO, e as pessoas com o Grupo B têm maior suscetibilidade à doença DM.

Anti-tumor activity of novel targeting HER2 antibody-drug conjugates / 药学学报

Antibody-drug conjugates (ADCs) are widely used in cancer treatment. Human epidermal growth factor receptor-2 (HER2) is overexpressed in various types of solid tumors and is a validated therapeutic target for cancers. To develop a more effective therapy, we generated a novel anti-HER2 humanized monoclonal antibody MIL40 and MIL40 drug conjugates as novel cancer therapies. The MIL40 was conjugated with small molecule cytotoxic agents DM1 [emtansine, N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine] or monomethylauristatin E (MMAE) to generate ADCs, which were evaluated for their in vitro and in vivo anti-cancer activities. Experimental results show that MIL40-DM1 and MIL40-MMAE can effectively identify and bind to HER2-positive tumor cells. The binding capabilities of MIL40-DM1 and MIL40-MMAE with HER2 extracellular domain (ECD) antigens were not different after conjugation with DM1 or MMAE. The ADCs showed potent cytotoxicity in HER2-positive ovarian cancer cells SKOV3, breast cancer cells SKBR3 and stomach cancer cells N87 in vitro. MIL40-DM1 can effectively inhibit the volume and weight growth of SKOV3 transplant tumors in mice. The mice in this study were used and treated by following the international guidelines for the care and use of laboratory animals, and approved by Animal Ethics Committee of Institute of Military Cognitive and Brain Sciences.

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment

Events including antibody‒antigen affinity, internalization, trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate (ADC) catabolism and hence the toxicity. Nevertheless, an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking. Considering the plethora of ADC candidates under development, we developed a target-responsive subcellular catabolism (TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest. We firstly applied TARSC to study the commercial T-DM1 and the biosimilar. We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences. Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further

Genome sequencing of Streptomyces aureofaciens DM-1 and analysis of 6-demethylchlortetracycline biosynthesis gene cluster / 生物工程学报

Streptomyces aureofaciens DM-1 is a high-yielding 6-demethylchlortetracycline producer. The genome sequencing of DM-1 reveals a linear chromosome containing 6 824 334 bps nucleotides with GC content of 72.6%. In this genome, a total of 6 431 open reading frames were predicted by using glimmer 3.02, Genemark and Z-Curve softwares. Twenty-eight secondary metabolite biosynthetic gene clusters were uncovered by using AntiSMASH gene prediction software, including the complete 6-demethylchlortetracycline biosynthetic gene cluster. A frame-shift mutation in methyltransferase coding region was detected, which may result in the demethylation of chlortetracycline. The complete genome sequence of S. aureofaciens DM-1 provides basic information for functional genomics studies and selection of high-yielding strains for 6-demethylchlortetracycline.

Single Dose Toxicity Study of Humanized Anti-HER2 Antibody Drug Conjugate in Rats / 中国药学杂志

OBJECTIVE: To conduct a single dose toxicology study of humanized anti-HER2 antibody drug conjugate for injection (HS630) and small molecular maytansine (DM1) in Sprague-Dawley rats. METHODS: Rats were divided randomly into nine groups including HS630 blank control group (0 mg•kg-1), DM1 vehicle control group (0 mg•kg-1), positive control group (Kadcyla®, 60 mg•kg-1), HS630 low-, middle-, high-dose groups (6, 20, 60 mg•kg-1) and DM1 low-, middle-, high-dose groups (0.10, 0.20, 0.40 mg•kg-1). Each group had twenty rats with female and male in half. Each rat was administered intravenously once. Animals were observed clinical symptoms consisting of behavior, fur and feces daily as well as body weight and food consumption twice or three times per week. Dissection was executed at D2 and D21 to examine gross anatomy with histopathological changes and weight main tissues. RESULTS: Rats given 60 mg•kg-1 HS630 appeared some adverse effects that 1/20 animal was dead. It was found that maximal tolerance dose of HS630 was 20 mg•kg-1 equivalent to 0.34 mg•kg-1 DM1. High dose could lead body weight and food consumption reduced and organ weights changed including liver, kidney, spleen and lung increased and testicle and epididymis decreased. Histopathological changes were observed in liver, spleen, lung, thymus, pancreas, kidney, mesenteric glands, intestinum, seminal vesicle, prostate, testicle, epididymis, adrenal gland, thyroid gland, pituitary body, eye, tongue, sternum (marrow), bone, skin, injection site. Rats given Kadcyla® showed the similar side effects with HS630. Rats given 20 mg•kg-1 HS630, abnormality weren′t observed in clinical symptom, body weight and food consumption. It could lead kidney and lung weighted. Histopathological changes were found in liver, spleen, thymus, pancreas, lung, kidney, mesenteric glands, duodenum, adrenal gland, pituitary body, skin. Rats given DM1 exhibited worse adverse effects that 2/20 animals were dead at 0.40 mg•kg-1 level. The maximal tolerance dose of DM1 was 0.20 mg•kg-1. High dose could lead body weight and food consumption reduced and organ weights changed including liver, spleen and adrenal gland increased and thymus decreased. Histopathological changes were found in liver, spleen, thymus, kidney, mesenteric glands, duodenum, intestinum, seminal vesicle, adrenal gland, pituitary body, eye, tongue, sternum (marrow), bone, skin. CONCLUSION: Rats given single dose of humanized anti-HER2 antibody-drug conjugate for injection (HS630) and chemical maytansine (DM1) respectively, the RESULTS: show that HS630, a kind of ADC products, have similar toxicological profile with Kadcyla® and exhibit better tolerability and wider safety margin when given the comparable dosage with DM1 based on the RESULTS: of tolerance, clinical symptoms, organ weight and histopathological findings.

Anti-HER2 Antibodies In Combination With Chemotherapy Or Chemotherapy-Free Regimens Targeting Her2-Positive Breast Cancer: A Systematic Review

@#Breast cancer is the leading cause of cancer-related death in female worldwide. Human epidermal growth factor receptor 2 (HER2) amplification is observed in approximately 20% of breast cancer cases and is associated with poor clinical outcomes. Dual HER2 blockade without chemotherapy represents an attractive therapeutic approach, and it remains unresolved if anti-HER2 therapeutic antibodies are sufficient to replace chemotherapy regimens. In this review, we discuss the approved therapeutic monoclonal antibodies (pertuzumab and trastuzumab) and antibody-drug conjugate (trastuzumab emtansine or T-DM1) for the treatment of HER2-positive breast cancer patients. In summary, phase II and III clinical trials have demonstrated that dual HER2 blockade (pertuzumab and trastuzumab) plus chemotherapy regimens confer better efficacy compared with dual HER2 blockade alone, or anti-HER2 antibody monotherapy, in HER2-positive breast cancer patients. Dual HER2 blockade (pertuzumab and trastuzumab) combined with chemotherapies (5-fluorouracil, epirubicin, cyclophosphamide and docetaxel) yield superior response. Moreover, dual HER2 blockade (T-DM1 and pertuzumab) in combination with docetaxel represents a promising treatment regimen containing T-DM1. Ongoing clinical trials are assessing the optimal chemotherapy of choice with anti-HER2 antibodies combinations. In conclusion, improved outcomes are attributable to selection for the optimal chemotherapy regimen in combination with anti-HER2 antibodies instead of replacing chemotherapy altogether with the current line of anti-HER2 therapeutic antibodies.

Biological effects of trastuzumab and T-DM1 on different breast cancer lines / 中国药学杂志

OBJECTIVE: To investigate the different biological effects of trastuzumab and T-DM1 on BT-474 and HCC1954 cell lines. METHODS: Flow cytometry was employed to study the expression level of HER2 on the two cell lines. ELISA was used to check the binding ability of trastuzumab and T-DM1 with HER2 antigen. With cell proliferation inhibition and killing methods, the dose-response curves were explored to demonstrate the biological effects of trastuzumab and T-DM1 on the two cell lines. RESULTS: HER2 were highly expressed in both of the two cell lines. The HER2 binding ability was highly similar between trastuzumab and T-DM1. Trastuzumab could inhibit the proliferation of BT474 but not HCC1954, while T-DM1 could kill both kinds of cells. CONCLUSION: In the in vitro cell models, T-DM1 can play biological effect in HER2 highly expressed but trastuzumab-resistant cell lines.

A novel HER2-targeted drug:T-DM1 antibody-drug conjugate / 中国肿瘤临床

T-DM1 is a novel antibody-drug conjugate that has similar biological activity with that of trastuzumab. T-DM1 specifically delivers DM1, the effective anti-microtubule drug, into the cytoplasm of tumor cells with HER2 overexpression. The efficacy of T-DM1 monotherapy is better than lapatinib in combination with capecitabine and T-DM and is expected to become the standard second-line treatment for HER2-positive advanced breast cancer drugs. Clinical trials that compare T-DM1 with trastuzumab joint taxane as the first-line of treatment for advanced breast cancer trials are currently being performed. T-DM1 is a brand new anti-HER2 drug after trastuzumab. U.S. FDA already approved T-DM1 as a drug for the treatment of HER2-positive advanced breast cancer patients.

Como a monitorização contínua de glicose subcutânea pode colaborar na interpretação dos valores da HbA1c no diabetes melito tipo 1?: [revisão] / How the continuous glucose monitoring system can contribute to HbA1c interpretation in type 1 diabetes mellitus?: [review]

O objetivo desta revisão é avaliar como o sistema de monitorização contínua de glicose subcutânea (CGMS®) pode colaborar na interpretação dos valores da hemoglobina glicada (A1c) no diabetes melito tipo 1. Foi realizada uma revisão bibliográfica dos benefícios, dos métodos, da interpretação e da experiência com CGMS®. A utilização de sensores contínuos pode ser útil na avaliação de pacientes com diabetes melito com oscilações glicêmicas, hipoglicemias graves, especialmente as noturnas, e hiperglicemias pós-prandiais. A identificação de padrões glicêmicos alterados permite ajustes terapêuticos e melhora do controle metabólico. O CGMS® é um procedimento de fácil utilização, com efeitos adversos de pequena intensidade e boa tolerância pelos pacientes. Embora o fabricante preconize um período de utilização de até três dias, observa-se que o prolongamento do teste por mais dias permite a obtenção de dados que auxiliam em mudanças terapêuticas superiores às realizadas com os registros do tempo convencional.

The aim of the present study is a literature revision of the contribution of continuous glucose monitoring system (CGMS®) in the interpretation of HbA1c levels in type 1 diabetes (T1DM). We performed a revision of the efficacy, benefits, interpretation of methods and experience with this system. The CGMS® could be useful in T1DM patients that present great glycemic variability or severe hypoglycemia (mainly nocturnal) and postprandial hyperglycemia. The identification of altered patterns or the glycemic variability allows therapeutic adjustment and improvement of the metabolic control. CGMS® is a safe method with a rare occurrence of side effects and it is well-tolerated by patients. The extension of the procedure for more days, over the 72h period recommended by the standard test, allows us to get important data to changes and adjustments on the insulin management of the type 1 diabetes mellitus patients.