Transmission electron microscopy of the retina following thyroidectomy in rabbit

Thyroid hormones play a crucial role in the neuroretinal maturation of the eye and central nervous system development. An experiment was conducted to survey the effects of thyroidectomy on rabbit retina. In this study, 10 male rabbits of New Zealand strips were divided into two groups of five animals each (control group and thyroidectomy group). Before surgery, the rabbits were maintained in 12-h light and 12-h dark. The animals were anesthetized with intraperitoneal injection of 10 mg/kg xylazine and 6 mg/kg ketamine, and bilateral thyroidectomy was performed. One and 2 weeks after surgery, the rabbits were sacrificed by humane methods. Then, retinas of the killed rabbits were isolated in the laboratory and examined by electron microscopy for evaluating cells and changes in inner segment, outer segment, outer limiting membrane, and outer nuclear layer. The result of this experiment showed vacuolization in inner section and endoplasmic reticulum of rabbit retina in group two. It was also observed that mitochondria of the inner segment of retina were larger and more circular than mitochondrial in control group; moreover, most of them had lost their crystal. The core in the control group was normal and had round to oval shape and distributed chromatin, but in thyroidectomy group, the mode of the nucleus was small and dark (pyknosis) and some nucleus had been destroyed.     

Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension

Key points

• Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.
• Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.
• Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.
• Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abstract

Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H₂O₂; 0.15 mmol l⁻¹). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H₂O₂ promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H₂O₂‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except with larger EAD amplitude. During the early stages of hypertension, when challenged with oxidative stress, SHR hearts showed an increased ventricular arrhythmogenicity that stems primarily from tissue remodelling (hypertrophy, fibrosis) rather than cellular electrophysiological changes. Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abbreviations

AP

action potential

APD

action potential duration

APD₉₀

action potential at 90% duration

CaMKII

calcium/calmodulin‐dependent protein kinase II

CaT

calcium transient

CaTD₉₀

calcium transient at 90% duration

CI

confidence interval

DBP

diastolic blood pressure

EAD/DAD

early/delayed after‐depolarization

HR

heart rate

ICC

interclass correlation

I_Ca,L

L‐type calcium current

I_Ks

slow delayed rectifier potassium current

I_Na

sodium current

I_to

transient outward potassium current

IVS(d,s) interventricular septum thickness (during diastole

during systole)

LV

left ventricle

LVEF

left ventricular ejection fraction

LVFS

left ventricular fractional shortening

LVH

left ventricular hypertrophy

LVID(d,s) left ventricular internal diameter (during diastole

during systole)

MV

mitral valve

NR

normotensive rats

PA peak vel

pulmonary artery peak velocity

(P)CL

(pacing) cycle length

PW

posterior wall

P‐ECG

pseudo‐electrocardiogram

RV

right ventricle

RWT

relative wall thickness

SHR

spontaneously hypertensive rats

SHHF

spontaneously hypertensive heart failure

SBP

systolic blood pressure

VT/VF

ventricular tachycardia and fibrillation

     

The Anti-Oxidant Effects of Ginger and Cinnamon on Spermatogenesis Dys-function of Diabetes Rats

Background

Diabetes rats have been linked to reproductive dysfunction and plant medicine has been shown to be effective in its treatment. Antioxidants have distinctive effects on spermatogenesis, sperm biology and oxidative stress, and changes in anti-oxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti-oxidants and have been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. The present study examined the influence of combined ginger and cinnamon on spermatogenesis in STZ-induced diabetes in male Wistar rats.

Materials and Methods

Animals (n = 80) were allocated randomly into eight groups, 10 each: Group 1: Control rats given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4: rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon) daily; Group 5: Diabetic control rats received only normal saline. Group 6: Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra-peritoneal injection of STZ in all groups. At the end of the experiment (56th day), blood samples were taken for determination of testosterone, LH,FSH, total anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis.

Results

Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased in ginger and cinnamon and combined ginger and cinnamon treated diabetic rats compared with control groups. Serum testosterone, LH and FSH were higher compared to control group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were increased at the end of treatment. Combined ginger and cinnamon showed more intense increase in all parameters compare to ginger and cinnamon alone. Most of the results were significant (P<0.05).

Conclusion

We concluded that combined ginger and cinnamon have significant beneficial effects on the sperm viability, motility, and serum total testosterone, LH,FSH and serum anti-oxidants'' level and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetics.     

Gene transfer efficiency of high primary amine content,hydrophobic, alkyl-oligoamine derivatives of polyethylenimine

In this study, a series of alkyl-oligoamine derivatives of low-toxicity 10 kDa polyethylenimine (PEI) were synthesized to enhance the hydrophobicity of PEI while preserving most of its primary amine content. PEI was reacted with a series of ω-bromoalkylcarboxylic acids with different chain lengths (2-bromoacetic, 6-bromohexanoic, 10-bromodecanoic and 16-bromohexadecanoic acids) to modify hydrophobicity followed by coupling to various oligoamines (spermine, spermidine, ethylendiamine or diethylentriamine) to partially restore primary amine density. These modifications were designed to influence hydrophobic–hydrophilic balance as well as maintain the proton sponge effect in order to create an efficient vector with low toxicity. Ethidium bromide exclusion assays and dynamic light scattering studies showed that the modified PEIs could bind to plasmid DNA and form nanoparticles in the range of 100 nm. The transfection efficiency of modified PEIs complexed with a luciferase reporter gene (pCMV-luc) in N2A murine neuroblastoma cells was increased to a level comparable to that of 25,000 Da PEI. These results indicate that hydrophobic modification of low-toxicity PEI without reduction in primary amine content is an effective strategy for improving transfection efficiency of polycation-based non-viral vectors while maintaining low toxicity.     

AAV-mediated persistent bevacizumab therapy suppresses tumor growth of ovarian cancer

Rationale

Anti-angiogenesis therapies such as bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), have been used against ovarian cancer, but transient and low peritoneal drug levels are likely a factor in treatment failure. We hypothesized that a single administration of adeno-associated virus (AAV)-mediated intraperitoneal expression of bevacizumab would direct persistent expression and suppress growth and metastasis of ovarian cancer.

Methods

AAVrh.10BevMab, a rhesus serotype 10 adeno-associated viral vector coding for bevacizumab, was evaluated for the capacity of a single intraperitoneal administration to persistently suppress peritoneal tumor growth in an intraperitoneal model of ovarian carcinomatosis with human ovarian cancer cells in nude immunodeficient mice.

Results

The data demonstrates that AAVrh10.BevMab mediates persistent and high levels of bevacizumab in the peritoneal cavity following a single intraperitoneal administration in mice. In AAVrh10.BevMab treated A2780 human ovarian cancer-bearing mice, tumor growth was significantly suppressed (p < 0.05) and the area of blood vessels in the tumor was decreased (p < 0.04). Survival of mice with A2780 xenografts or SK-OV3 xenografts was greatly prolonged in the presence of AAVrh10.BevMab (p < 0.001). Administration of AAVrh10.BevMab 4 days after A2780-luciferase cell implantation reduced tumor growth (p < 0.01) and increased mouse survival (p < 0.0001). Combination of AAVrh10.BevMab with cytotoxic reagents paclitaxel or topotecan proved to be more effective in increasing survival than treatment with cytotoxic reagent alone.

Conclusion

A single administration of AAVrh10.BevMab provides sustained and high local expression of bevacizumab in the peritoneal cavity, and significantly suppresses peritoneal carcinomatosis and increases survival in an ovarian cancer murine model.     

Evaluating the Prevalence of PTSD among Children and Adolescents after Earthquakes and Floods: a Systematic Review and Meta-Analysis

Psychiatric Quarterly - Our study systematically reviews articles about the prevalence of Post-traumatic Stress Disorder (PTSD) among children and adolescents, aiming to evaluate its prevalence...