Therapeutic Dose of Hydroxyurea-Induced Synaptic Abnormalities on the Mouse Spermatocyte

Hydroxyurea (HU) is a widely used pharmacological therapy for sickle cell disease (SCD). However, replication stress caused by HU has been shown to inhibit premeiotic S-phase DNA, leading to reproductive toxicity in germ cells. In this study, we administered the therapeutic doses of HU (i.e., 25 and 50 mg/kg) to male mice to explore whether replication stress by HU affects pachytene spermatocytes and causes the abnormalities of homologous chromosomes pairing and recombination during prophase I of meiosis. In comparison with the control group, the proportions of spermatocyte gaps were significantly different in the experimental groups injected with 25 mg/kg (p < 0.05) and 50 mg/kg of HU (p < 0.05). Moreover, the proportions of unrepaired double-stranded breaks (DSBs) observed by γH2AX staining also corresponded to a higher HU dose with a greater number of breaks. Additionally, a reduction in the counts of recombination foci on the autosomal SCs was observed in the pachytene spermatocytes. Our results reveal that HU has some effects on synaptonemal complex (SC) formation and DSB repair which suggest possible problems in fertility. Therefore, this study provides new evidence of the mechanisms underlying HU reproductive toxicity.

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The Safety of Viscum Album L. in A Murine Model: A Reproductive Toxicity Study

10.21203/rs.3.rs-39354/v1 ◽

2020 ◽

Author(s):

Ricardo Ghelman ◽

Mirlene Cecília Soares Pinho Cernach ◽

Marcia Marcelino de Souza Ishigai ◽

Jorge Kioshi Hosomi ◽

Manuel de Jesus Simões ◽

...

Keyword(s):

Therapeutic Dose ◽

Dose Group ◽

Reproductive Toxicity ◽

Viscum Album ◽

High Dose Group ◽

Control Group ◽

High Dose ◽

Pregnant Rats ◽

Usual Therapeutic Dose ◽

Therapeutic Doses

Abstract Background: The use of antineoplasic drugs in pregnancy poses a huge safety challenge because of the risk of teratogenicity, mutagenicity and carcinogenicity. The rational use of the herbal medicine Viscum album (VA) has shown promising results in several tumor lines as part of the strategy of immunotherapy and anti-angiogenesis in integrative oncology. The safety of intrauterine fetal exposure to VA is however unknown and can be further evidenced for therapeutic doses in pregnant cancer patients.Methods: 47 pregnant Wistar rats and 399 fetuses bred following exposure to VA were investigated. The rats were randomized into five groups. Control group (CG) received no treatment and stress group (SG) received daily vehicle subcutaneous injections alone in same volume as the treatment groups from day zero until the twentieth day of pregnancy. There were three treatments groups: therapeutic dose group (TG) received the usual therapeutic dose (UTD) of 0.013 mg/kg BW; high dose group (HG) received 12.5 mg/kg BW and very high dose group (VHG) received 25mg/kg BW, daily.Results: Weight gain was greater in the rats, placentas and fetuses in the TG and HG compared to SG. Histology of the placentas showed a greater inflammatory process in HG and VHG.Conclusion: Since no cases of abortion, embryotoxicity, natimortality or teratogenicity were found in the fetuses and histology detected no lesions in the tissues evaluated, it is reasonable to conclude that this drug is safe for use in pregnant rats.

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Hexachlorobenzene toxicity in the monkey ovary: III. Ultrastructure induced by high (10 mg/kg) dose exposure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084958 ◽

1991 ◽

Vol 49 ◽

pp. 130-131

Author(s):

A. Singh ◽

A. Dykeman ◽

J. Jarrelf ◽

D. C. Villeneuve

Keyword(s):

Present Report ◽

Reproductive Toxicity ◽

Control Group ◽

Primate Model ◽

Human Follicular Fluid ◽

Thin Sections ◽

Cynomolgus Monkeys ◽

Cacodylate Buffer ◽

Induction Cycle ◽

Comprehensive Study

Hexachlorobenzene (HCB), a persistent and mobile organochlorine pesticide, occurs in environment. HCB has been shown to be present in human follicular fluid. An objective of the present report, which is part of a comprehensive study on reproductive toxicity of HCB, was to determine the cytologic effects of the compound on ovarian follicles in a primate model.Materials and Methods. Eight Cynomolgus monkeys were housed under controlled conditions at Animal facility of Health and Welfare, Ottawa. Animals were orally administered gelatin capsules containing HCB mixed with glucose in daily dosages of 0.0 or 10 mg/kg b.w. for 90 days; the former was the control group. On the menstrual period following completion of dosing, the monkeys underwent an induction cycle of superovulation. At necropsy, one-half of an ovary from each animal was diced into ca. 2- to 3-mm cubed specimens that were fixed by immersion in 2.5% glutaraldehyde in 0.1 M cacodylate buffer (pH 7.3). Subsequent procedures followed to obtain thin sections that were examined in a Hitachi H-7000 electron microscope have been described earlier.

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Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽

10.1182/blood.v71.3.597.597 ◽

1988 ◽

Vol 71 (3) ◽

pp. 597-602 ◽

Cited By ~ 18

Author(s):

GP Rodgers ◽

MS Roy ◽

CT Noguchi ◽

AN Schechter

Keyword(s):

Blood Flow ◽

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Microvascular Obstruction ◽

Controlled Study ◽

Control Group ◽

Cell Disease ◽

Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

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ECT rekindles pharmacological response in schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2009.04.005 ◽

2009 ◽

Vol 24 (8) ◽

pp. 521-525 ◽

Cited By ~ 16

Author(s):

H. Hustig ◽

R. Onilov

Keyword(s):

Small Sample Size ◽

Antipsychotic Agents ◽

Pharmacological Therapy ◽

Small Sample ◽

Clinical Population ◽

Control Group ◽

Clinical Notes ◽

Symptom Profiles ◽

Pharmacological Response ◽

Maintenance Ect

AbstractObjectiveThe aim of our naturalistic-observational study was to determine the efficacy and utility of electroconvulsive therapy (ECT) in clinical population of individuals with schizophrenia where pharmacological response was suboptimal.MethodsThe cohort comprised 27 patients suffering from schizophrenia with refractoriness to antipsychotic agents and with severe, disabling symptoms. They only interventional assessing tool was clinical global impression (CGI-S) performed at the baseline and at the end of the treatment.ResultsThe administration of ECT resulted in overall clinical improvement reflected in CGI scales and descriptions in clinical notes. On 12 months follow-up period, 10 patients (37.1%) maintained improvement and were able to continue with pharmacological therapy only, suggesting its rekindling effect, especially with Clozapine. Conversely, 17 patients (62.9%) deteriorated and required an additional course of ECT to maintain improvement. In some cases, maintenance ECT treatment was required. The group who engaged in self-harming behaviour at baseline demonstrated they were more likely to relapse into psychosis at the end of the first course of ECT, their self-harming behaviour abated, especially when maintenance ECT was undertaken.ConclusionsAlthough limited by lack of control group, small sample size, heterogeneous symptom profiles and various concurrent neuroleptic agents, the ECT proved as valuable and safe augmentative procedure when unsatisfactory response to pharmacological interventions had been demonstrated prior to interventions. This effect was evident despite the chronicity of the illness.

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Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint

Nucleic Acids Research ◽

10.1093/nar/gks1016 ◽

2012 ◽

Vol 41 (1) ◽

pp. 229-241 ◽

Cited By ~ 21

Author(s):

Elisa Zucca ◽

Federica Bertoletti ◽

Ursula Wimmer ◽

Elena Ferrari ◽

Giuliano Mazzini ◽

...

Keyword(s):

Dna Polymerase ◽

Replication Stress ◽

S Phase ◽

Human Dna ◽

Dna Polymerase Λ ◽

Synthetically Lethal ◽

S Phase Checkpoint

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Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to facilitate DNA damage repair and recovery from replication stress

Biochemical Pharmacology ◽

10.1016/j.bcp.2006.11.014 ◽

2007 ◽

Vol 73 (6) ◽

pp. 760-772 ◽

Cited By ~ 25

Author(s):

Z. Ping Lin ◽

Michael F. Belcourt ◽

Rocco Carbone ◽

Jana S. Eaton ◽

Philip G. Penketh ◽

...

Keyword(s):

Dna Damage ◽

Ribonucleotide Reductase ◽

Dna Damage Repair ◽

Replication Stress ◽

S Phase ◽

Damage Repair ◽

Ribonucleotide Reductase R2 ◽

S Phase Checkpoint

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Assessment of 25 Hydroxy Cholecalceferol Level in Autistic Children; is there a role for it in Treatment of Autism Spectrum Disorder?

QJM ◽

10.1093/qjmed/hcab113.039 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Martina Alfred Youssef Nakhla ◽

Eman Ahmed Zaky ◽

Enas Samir Nabeh ◽

Asmaa Wafeeq Abd El Aziz

Keyword(s):

Vitamin D ◽

Serum Vitamin ◽

Autism Spectrum ◽

Laboratory Evaluation ◽

Control Group ◽

Autistic Children ◽

Serum Vitamin D ◽

Group I ◽

Egyptian Children ◽

Therapeutic Doses

Abstract Background Autism is a group of neurodevelopmental disabilities with various genetic and environmental risk factors. Vitamin D is an important neurosteroid hormone which can affect brain development and function, but research on its use in treating autism has been limited. Objectives The current study aimed at assessing the level of 25 OH vit D3level in a group of autistic infants and children compared to controls and correlating it with the severity of autistic manifestations and evaluation of the role of therapeutic doses of vitamin D on the severity of autistic manifestations. Methodology Thirty autistic Egyptian children (group I) and 30 clinically healthy age and sex matched controls were enrolled (group II). Therapeutic doses of vitamin D were given for autistic children who showed insufficient levels of 25 OH cholecalceferol for a period of 4-6 weeks followed by maintenance doses for another 6 weeks. Psychometric and laboratory evaluation for this group was done thrice: at the onset of study, at 6 week after enrollment in the study, and at 12 weeks after that enrollment. Results Serum vitamin D level was substantially reduced in patients with ASD in comparison to control group, and on the other hand, 25 (OH) vitamin D level was significantly negatively correlated with ATEC score and Total CARS score. Autistic children who received vitamin D3 treatment had significant improvement of CARS and ATEC scores. Conclusion vitamin D supplementation significantly improved the outcome of enrolled autistic children. It is recommended to follow up our studied sample to check the consolidation of improvement for how long it will be needed.

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PainVision® Apparatus for Assessment of Efficacy of Pulsed Radiofrequency Combined with Pharmacological Therapy in the Treatment of Postherpetic Neuralgia and Correlations with Measurements

BioMed Research International ◽

10.1155/2017/5670219 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Dong Wang ◽

Kai Zhang ◽

ShaoLong Han ◽

LingZhi Yu

Keyword(s):

Pain Intensity ◽

Postherpetic Neuralgia ◽

Breakthrough Pain ◽

Short Form ◽

Persistent Pain ◽

Pharmacological Therapy ◽

Control Group ◽

Mcgill Pain Questionnaire ◽

Pulsed Radiofrequency ◽

Highly Correlated

Objective. PainVision device was a developed application for the evaluation of pain intensity. The objective was to assess the efficacy and safety of pulsed radiofrequency (PRF) combined with pharmacological therapy in the treatment of postherpetic neuralgia (PHN). We also discussed the correlation of the measurements.Method. Forty patients with PHN were randomized for treatment with PRF combined with pharmacological therapy (PRF group,n=20) or pharmacological therapy (control group,n=20) at postoperative 48 hours. The efficacy measure was pain degree (PD) that was assessed by PainVision and visual analog scale (VAS), short form Mcgill pain questionnaire (SF-Mcgill), and numeric rate scale sleep interference score (NRSSIS). Correlations between PD, VAS, SF-Mcgill, and NRSSIS were determined.Results. The PD for persistent pain (PP) and breakthrough pain (BTP) at postoperative 48 hours assessed by PainVision were significantly lower in PRF group than in control group (PD-PP,P<0.01; PD-BTP,P<0.01). PD and VAS were highly correlated for both persistent pain (r=0.453,ρ=0.008) and breakthrough pain (r=0.64,ρ=0.001).Conclusion. PRF was well tolerated and superior to isolated pharmacological therapy in the treatment of PHN. PainVision device showed great value in the evaluation of pain intensity and PD had an excellent correlation with VAS and SF-Mcgill.

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Efektivitas Slow Stroke Back Massage Dengan Minyak Aromaterapi Lavender Terhadap Penurunan Nyeri Penderita Kanker Serviks

Medica Hospitalia : Journal of Clinical Medicine ◽

10.36408/mhjcm.v6i1.376 ◽

2019 ◽

Vol 6 (1) ◽

pp. 35-39

Author(s):

Sri Setyowati ◽

Anik Rakhmawati ◽

Sumarsih Sumarsih ◽

Maria Indri Wigatiningsih

Keyword(s):

Cervical Cancer ◽

Cancer Patients ◽

Intervention Group ◽

Pharmacological Therapy ◽

Wilcoxon Test ◽

Bivariate Analysis ◽

Control Group ◽

Purposive Sampling ◽

Randomized Control ◽

Back Massage

Pain is one of the main complaints of patients with Cervical cancer patients caused due to tumor growth, infiltrats, the effects of repeated diagnostics and treatment procedures. The types of treatment which are often given to the patients are pharmacological therapies or drugs, which can provide many side effects when used in the long term. This study aimed to know the effects of slow stroke back massage technique combined with lavender aromaterapy oil to reduce pain in patients with Cervical cancer in Dr. Kariadi Hospital. This study was a quantitative quasi experiment with randomized control group pretest-posttest design. The sampling was purposive sampling. The study involved 15 participants in the intervention group and 15 participants in the control group. The data were analyzed by univariate and bivariate analysis using wilcoxon test. The results showed that there were reduction of pain in the intervention groups with p = 0.000. This study revealed that slow stroke back massage technique combined with lavender aromaterapy oil techniques as a non-pharmacological therapy provided an effect on the decrease of pain in cervical cancer patients. Based on the study, it is suggested that nurses apply slow stroke back massage technique combined with lavender aromaterapy oil techniques as a non-pharmacological therapy to reduce pain in cervical cancer patients. Keywords: Pain, cervical cancer, slow stroke back massage, lavender aromaterapy oil Nyeri adalah salah satu keluhan utama pada pasien kanker serviks disebabkan karena pertumbuhan tumor, infiltrat di tempat lain, efek dari prosedur diagnostik dan perawatan yang berulang. Penanganan nyeri yang sering kali diberikan adalah pemberian terapi farmakologi atau obat-obatan yang memberikan banyak efek samping apabila digunakan dalam jangka waktu lama. Penelitian ini bertujuan untuk mengetahui pengaruh teknik slow stroke back massage dengan minyak aromaterapi lavender terhadap penurunan nyeri pada pasien kanker serviks di RSUP Dr Kariadi Semarang. Penelitian ini merupakan penelitian kuantitatif quasy eksperimental dengan metode randomized control group pre test posttest design. Pengambilan sampel dilakukan dengan teknik purposive sampling yaitu 15 responden sebagai kelompok intervensi dan 15 responden sebagai kelompok kontrol. Analisa data dilakukan secara bivariat dan univariat dengan menggunakan uji wilcoxon. Hasil penelitian menunjukkan terdapat perbedaan penurunan nyeri pada kelompok intervensi yang diberikan terapi slow stroke back massage dengan aromaterapi lavender dengan nilai p=0.000. Kesimpulan penelitian ini membuktikan bahwa teknik slow stroke back massage dengan minyak aromaterapi lavender sebagai terapi non farmakologis berpengaruh terhadap penurunan nyeri pada pasien kanker serviks. Saran: perawat diharapkan mengaplikasikan teknik slow stroke back massage dengan minyak aromaterapi lavender sebagai terapi non farmakologis untuk menurunan nyeri pada pasien kanker serviks. Kata kunci: Nyeri, Kanker Serviks, slow stroke back massage, minyak aromaterapi lavender

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Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

10.21203/rs.3.rs-24673/v1 ◽

2020 ◽

Author(s):

Guiqing Zhou ◽

Jianhui Liu ◽

Xiangyang Li ◽

Yujian Sang ◽

Yue Zhang ◽

...

Keyword(s):

Cytochrome C ◽

Silica Nanoparticles ◽

Caspase 3 ◽

Reproductive Toxicity ◽

Control Group ◽

Caspase 9 ◽

Protein Expressions ◽

Underlying Mechanisms

Abstract Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

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