Mechanical evaluation of the effect of the rod to rod distance on the stiffness of uniplanar external fixator frames.

PURPOSE: To investigate the effect of the rod-to-rod distance on the mechanical stability of single-rod and double-rod external fixator frames. METHODS:  Four different constructs, one single-rod and three double-rod constructs with different rod-rod distances, were subjected to the axial, bending, and torsional forces. The stiffness of different configurations was calculated. RESULTS:  Single-rod configuration had statistically the lowest stiffness when subjected to the axial, bending, and torsional forces. Maximum stiffness against the axial and anterior-posterior bending forces was achieved when the rod-rod distance was adjusted to 50 mm (halfway between the first rod and the end of the Schanz pins). There was no statistically significant difference in lateral bending stiffness among different double-rod configurations (p value: 0.435). The maximum stiffness against torsional forces was achieved when the rod-rod distance was adjusted to 100 mm (the second rod at the end of the Schanz pins). CONCLUSION:  Double-rod uniplanar external fixator frames are significantly stiffer than the single-rod constructs, and however, the rod-rod distance can significantly affect the construct stiffness. We found that a frame with 50 mm rod-rod distance was the optimum fixator among tested configurations that allowed a balance between axial, bending, and torsional stiffness of the construct.

Dislocation of Rotating Hinged Knee Prostheses in a Patient With Extensor Mechanism Dysfunction.

Rotating hinged knee replacements are used to restore knee stability when intrinsic stability is lost in the form of soft tissue compression. With medical engineering advancements and improvements in arthroplasty, intrinsic stability can be achieved by an implant post system. We present the case of a 44-year-old female who presented with post-traumatic right knee multi-ligamentous instability and advanced secondary osteoarthritis following a traumatic knee dislocation two years ago. The patient initially underwent a hinged total knee replacement. After five years, she got dislocation of hinged total knee replacement that affected her condition and necessitated emergency admission for open reduction and revision. Most reported cases of rotating hinge prosthesis dislocation occurred during the first year of follow-up. However, our case dislocated after five years of follow-up due to dislodgement from the tibial tray with the polyethylene channel in the form of fatigue failure of the anti-dislocation mechanism.

Evaluating the Current Practice of Post Cesarean Thromboprophylaxis and Enhancing Guideline Adherence in Al-Najaf Hospitals.

BACKGROUND: Venous thromboembolism (VTE) is one of the most common cardiovascular disorders in the United States and is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE) which represented as the most important cause of death in pregnant women after cesarean section. Venous thromboembolism (VTE) is representing the second direct cause of death which is accounting for 13.8% of all mother's death in the world. The most common risk factor of venous thromboembolism (VTE) is cesarean section. OBJECTIVE: The study aims to study the current practice of post-cesarean thromboprophylaxis in dosing calculation and duration of therapy. METHODS: Between September 2020 and January 2021, an observational- interventional prospective pre and post-study, was conducted in all hospital of Najaf in the City center and the suburbs that contain gynecology and obstetric ward to assess the current practice of post-cesarean thromboprophylaxis and to evaluate the impact of pharmacist intervention program to improve guideline adherence then after intervention. Another 102 patients were enrolled to analyze the change thromboprophylaxis according to the guideline. RESULTS: From patient data, the rate of adherence to guidelines raised significantly among the post-intervention patients' group by thromboprophylaxis dose according to body weight was increase significantly (p<0.001) from 56.9% in the observation phase to 83.3% after intervention and about the duration of thromboprophylaxis is significantly (p<0.001) from 18.6% in the observation phase to 52.0% after the intervention. CONCLUSION: This study showed that the clinical pharmacist's multifaceted intervention has resulted in encouraging guideline implementations as reflected by improving the proper use of thromboprophylaxis the duration anddosing calculations according to body weight.

Gene therapy and erectile dysfunction: the current status.

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.

Gene therapy and erectile dysfunction: the current status / 亚洲男科学杂志(英文版)

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e. sildenafil, tadalafil and vardenafil) has revolutionized the treatment of ED, these oral medications require on-demand access and are not as effective in treating ED related to diabetic, post-prostatectomy and severe veno-occlusive disease states. Improvement in the treatment of ED is dependent on understanding the regulation of human corporal smooth muscle tone and on the identification of relevant molecular targets. Future ED therapies might consider the application of molecular technologies such as gene therapy. As a potential therapeutic tool, gene therapy might provide an effective and specific means for altering intracavernous pressure "on demand" without affecting resting penile function. However, the safety of gene therapy remains a major hurdle to overcome before being accepted as a mainstream treatment for ED. Gene therapy aims to cure the underlying conditions in ED, including fibrosis. Furthermore, gene therapy might help prolong the efficacy of the PDE5 inhibitors by improving penile nitric oxide bioactivity. It is feasible to apply gene therapy to the penis because of its location and accessibility, low penile circulatory flow in the flaccid state and the presence of endothelial lined (lacunar) spaces. This review provides a brief insight of the current role of gene therapy in the management of ED.

The role of serotonin (5-hydroxytryptamine1A and 1B) receptors in prostate cancer cell proliferation.

PURPOSE: Serotonin (5-hydroxytryptamine), a monoamine neurotransmitter released by prostate neuroendocrine cells, has a fundamental role in tumor growth, differentiation and gene expression. We investigated the effect of 5-hydroxytryptamine and 5-hydroxytryptamine antagonists on the growth of prostate cancer cells and we identified 5-hydroxytryptamine receptor expression in PC3 cells and in human hormone refractory prostate cancer tissue. MATERIALS AND METHODS: A total of 12 preparations of hormone refractory PC3 human prostate cancer cells were incubated with 5-hydroxytryptamine, or the 5-hydroxytryptamine receptor antagonists 5-hydroxytryptamine1A, 1B, 1D, 2, 3 or 4. After 72 hours cell viability was assessed using the crystal violet assay. PC3 cells treated with 5-hydroxytryptamine1A and 1B antagonists were investigated for apoptosis using flow cytometry. PC3 cells and sections of hormone refractory human prostate cancer tissue were studied by immunohistochemistry and Western blot analysis. RESULTS: In PC3 cells 5-hydroxytryptamine caused dose dependent proliferation with a maximum increase of 15% in 12 preparations at a concentration of 10(-8) M at 72 hours compared to controls (p < 0.0001). At a concentration of 10(-4) M at 72 hours the 5HT1A antagonist NAN-190 hydrobromide and the 5-hydroxytryptamine1B antagonist SB224289 HCl (Tocris Laboratories, Bristol, United Kingdom) induced a 20% and 78% inhibitory effect, respectively, on PC3 cell growth compared to that in controls (p < 0.0001). In PC3 cells 5-hydroxytryptamine1A and 1B antagonists demonstrated apoptosis after 24 and 48 hours of incubation. Immunostaining for 5-hydroxytryptamine1A and 1B receptors was seen in PC3 cells and prostate cancer tissue. Western blot analysis demonstrated 5-hydroxytryptamine1A and 1B receptor proteins with 46 and 43 kDa bands, respectively. CONCLUSIONS: In PC3 prostate cancer cells 5-hydroxytryptamine1A and to a greater extent 5-hydroxytryptamine1B antagonists significantly inhibit growth and induce apoptosis. To our knowledge growth inhibition caused by the 5-hydroxytryptamine1B antagonist SB224289 HCl is a novel finding, as is apoptosis caused by the 2 antagonists 5-hydroxytryptamine1A and 1B. This effect is most likely mediated via 5-hydroxytryptamine1A and 1B receptors. Therefore, our results imply that 5-hydroxytryptamine1A and in particular 5-hydroxytryptamine1B receptor antagonists warrant further investigations as potential anti-neoplastic agents.

Pharmacological properties of endothelin-1 in the rabbit corpus cavernosum.

BACKGROUND: Endothelin (ET-1) may play a role in the regulation of erection but this has not been conclusively demonstrated. Augmented cavernosal smooth muscle (CSM) contraction in the rat occurs following exposure to both ET-1 and phenylephrine (PE; alpha-1 agonist). The aim of this study was to assess the effect of ET-1 and its possible role in the alpha1-adrenergic pathway during the erectile process. MATERIALS AND METHODS: Organ bath studies were performed on CSM strips of penises obtained from 12 age-matched New Zealand White rabbits. The effect of ET-1 and PE alone on CSM tone in the absence and presence of ETA (BQ123) and ETB (BQ788) antagonists was assessed. Tissue responses were measured as tension (newton, N). EC50 values are expressed as mean +/- S.E.M. RESULTS: PE (10(8) - 10(-4) M) and ET-1 (10(-10) - 10(-6) M) produced a concentration-dependent contraction in rabbit CSM strips. The EC50 values were 1.7 x 10(-7) M +/- 1.1 and 3.4 x 10(-9) M +/- 1.5, respectively. BQ123 10(-5) M significantly inhibited ET-1-mediated CSM contractions more than BQ788 10(-5) M (both ANOVA p<0.01). The EC50 were 1.3 x 10(-6) M +/- 2.6 and 2.0 x 10(-7) M +/- 2.1, respectively. Neither the ETA or ETB receptor antagonist had a significant influence on alpha1-adrenergic receptor-mediated CSM contraction. CONCLUSION: ETA receptors may play a greater role than ETB receptors in ET-1-induced rabbit CSM contraction and the detumescence process. The a1-adrenergic-dependent pathway does not involve the ETA or ETB receptors.

The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation.

OBJECTIVE: To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3). MATERIALS AND METHODS: HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3) and 5HT(4)). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS: 5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10(-8)m as compared to the control at 72 h. At 10(-4)m, 5HT(1A) antagonist (NAN-190 hydrobromide) and 5HT(1B) antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT(1A) and 5HT(1B) receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT(1A) and 5HT(1B) receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION: 5HT(1A) and to a greater extent 5HT(1B) antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT(1A) and 5HT(1B) receptors. These results highlight the potential use of 5HT(1A) and 5HT(1B) antagonists in the treatment of bladder cancer.

The role of serotonin in tumour growth (review).

Serotonin (5-hydroxytryptamine; 5HT) a monoamine neurotransmitter mediates a wide range of physiological actions in the human body. For example 5HT is implicated in psychiatric and neurological disorders and also plays a fundamental role in tumour growth, differentiation and gene expression. 5HT acts as a growth factor for several types of tumoural and non-tumoural cells. This review considers the role of 5HT and its receptors in the human body with particular reference to carcinogenesis. We conclude that 5HT causes growth proliferation and 5HT antagonists cause growth inhibition in a variety of tumour cells (e.g. prostate carcinoma, lung carcinoma and colonic carcinoma). Therefore, further studies should look into the potential use of 5HT antagonists in the treatment of cancer.

Growth inhibitory effect of doxazosin on prostate and bladder cancer cells. Is the serotonin receptor pathway involved?

UNLABELLED: Doxazosin, an alpha1-adrenoceptor antagonist, is used for the treatment of benign prostatic hyperplasia (BPH) and hypertension. Alpha-adrenoceptor antagonists also inhibit growth and induce apoptosis in malignant prostatic cells. The apoptotic activity is independent of their capacity to antagonize alpha-adrenoceptors. The effect of doxazosin on the growth of prostate and bladder cancer cell lines was assessed and whether the growth inhibitory effect of doxazosin on prostate cancer cells is serotonin (5-hydroxtryptamine; 5HT)-dependent was investigated. MATERIALS AND METHODS: PC3 (androgen-independent prostate cancer) and HT1376 (grade III transitional cell carcinoma) cells were plated. The cells were incubated with doxazosin. After 72 h, cell viability was assessed (crystal violet assay). Studies were also performed after incubating the PC3 cells with 5HT or 5HT(1B) agonists for a short duration, followed by the addition of doxazosin. Cell viability was assessed at 72 h. RESULTS: Doxazosin caused a dose-dependent inhibition of PC3 and HT1376 cell growth with a maximum inhibition of 80% (n=12, p < 0.0001) and 91% (n=12, p < 0.0001), respectively, at a concentration of 10(-4)M, at 72 h. Incubation of PC3 cells with 5HT or 5HT(1B) agonist, followed by addition of doxazosin, increased the percent of viable cells as compared to when the cells were treated with doxazosin alone. CONCLUSION: Doxazosin significantly inhibited prostate (PC3) and bladder cancer (HT1376) cell growth. Furthermore, prior incubation of PC3 cells with 5HT or 5HT(1B) agonist increased cell viability as compared to treatment with doxazosin alone. These findings may be related to the similarity between subtype 1 serotonin and adrenergic receptors. The effect of alpha1-adrenoceptor antagonists on tumour cell growth merits further investigation.