Feasibility of drug delivery to the eye’s posterior segment by topical instillation of PLGA nanoparticles

We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles(NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan(CS) and glycol chitosan(GCS), which are mucoadhesive polymers, and polysorbate 80(P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells.Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal,non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.

Intravesical Non-Alkalinized Lidocaine Instillation for Interstitial Cystitis/Bladder Pain Syndrome Patients

Purpose: The effectiveness of daily or weekly instillation of non-alkalinized lidocaine for patients suffering interstitial cystitis and/or bladder pain syndrome was evaluated retrospectively. Patients and methods: Five female patients (40 - 71 years old) diagnosed as interstitial cystitis by cystoscopic findings and a 68 year-old bladder pain syndrome patient were enrolled. All patients, having interstitial cystitis, had undergone hydrodistention therapy previously and had not improved their symptoms by empirical therapies. Daily or weekly (upon their severity of symptoms) intravesical instillation of 20 ml of 4% non-alkalinized (pH 6.0 - 7.0) lidocaine solution was performed for several times, and patients were asked to keep them in the bladder as long as two hours each time. Previous medications such as anti-cholinergic drugs and analgesics were continued according to patient's requirements and symptoms. The treatment effect was evaluated comparing O'Leary-Sant Symptom Index for interstitial cystitis patients and visual analog pain scale before and after the series of lidocaine therapies. Results: Instillation was made 6 to 16 times. Patients with interstitial cystitis improved their symptoms from O'Leary-Sant Symptom Index 17.5 to 10, Problem Index from 14.8 to 6 in an average. Crouching pain disappeared in all these patients after the instillation therapy. Severe interstitial cystitis findings on cystoscopy disappeared completely in one patient after the therapy. One patient having bladder pain syndrome reduced her analgesics use, and bladder-filling pain decreased from 7 to 3 as a visual analog scale score. One patient complained palpitation at 11th instillation and abandoned treatment thereafter, otherwise, none of these patients showed side effect concerning lidocaine toxicity. Conclusions: Intravesical non-alkalinized lidocaine instillation therapy for interstitial cystitis/bladder pain syndrome patients were an easy, safe and effective treatment.

Intravesical Instillation in Pure Line LEW Rats and Nude Mice

In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and an- gle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activi- ties of animals weren’t influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

A Five-year Follow-up Study on the Efficacy and Safety of Female Tubal Sterilization by Chemical Instillation

A multi center randomized clinical trial was adopted in the present study. 1705 eligible women with identical demographic and gynecological characteristics were divided into two groups: 871 using phenol atabrine paste (PAP) and 834 using phenol mucilage (PM). The five year follow up rates for the two groups were 97.5% and 98.1%, respectively. The multiple decrement life table analysis showed that there was a significant difference in the gross cumulative failure rates between the two groups. The 60th month gross cumulative failure rates for PAP group and PM group were 4.61% and 11.87%, respectively, thus indicating the efficacy of PAP to be significantly higher than that of PM. 97.7% users had cervical smear examinations, but no suspected cancer cells or cancer cells were found. Meanwhile, there was no known diseases related to the chemical reagent. This follow up study indicates that tubal sterilization by chemical instillation is a simple,safe and efficient female method. It suggested that this method would be introduced to a wider use on the basis of modification in the composition of chemical agents, standardized operational procedure, and improved administrative regulation in the use of this technology.

Effect of Ketamine Instillation on Acute and Chronic Post Mastectomy Pain, a Dose Finding Clinical Study

Background: Uncontrolled acute postoperative pain is considered a risk factor for the development of chronic pain afterward. Objectives: To explore the most effective dose of ketamine instillation (1 of 3 doses: 1, 2, or 3 mg/kg) for acute and chronic post mastectomy pain (PMP). Methods: Ninety female patients with cancer breast, aged (18 - 60 yrs), weighted (50 - 90 kg), scheduled for modified radical mastectomy, randomly allocated into 3 groups to receive ketamine instillation after surgical homeostasis before wound closure (1 of 3 doses;1, 2, or 3 mg/kg as A, B or C groups respectively) patients were followed up for 48 h for acute pain (total morphine consumption, the first request of analgesia and visual analog scale at rest and movement (VASR/M), chronic pain by Leeds assessment of neuropathic signs and symptoms (LANSS) for six-months, hemodynamics, and side effects. Results: Median total dose of morphine consumption was 8 mg (5 - 10) versus 6 mg (6 - 7) in A and B groups respectively in the first 48 h postoperatively. Lowest VASR/M was recorded in C then B and lastly A group (P = 0.037). No patients in the C group requested analgesia versus thirty (100%) and nine (30%) patients in the A and B groups respectively with the first request of analgesia was 12 h (5 - 36) in the A group versus 30 h (12 - 36) in the B group respectively (P Conclusion: Ketamine instillation effectively controlled acute post mastectomy pain (PMP) in a dose-dependent manner and reduced the incidence and severity of chronic pain in patients who undergoing a modified radical mastectomy.

Technical Evaluation of Eye Drops Instillation： A Systematic Review

Objective： Assess the profile of eye drops in patients with eye diseases. Methods： Studies available in the scientific literature were identified without any time limits using the databases Embase-Medline, Scielo, Scopus and Web of Knowledge. The selected studies were compared with the following inclusion criteria： （i） if the study evaluated the eye drop instillation, （ii） if the study involved participation of patients with eye diseases. Results： Twelve studies met the inclusion criteria. Of them, 83.33% evaluated the technique of eye drop instillation in patients with glaucoma, 8.33% in patients with eye diseases and 8.33% in patients with cataract after undergoing surgery to correct. 41.66% of studies have chosen to record a video of patients to analyze the technique of instilling eye drops and 41.66% did not describe the/esearch location. Regarding the type of study, 75% had the design as prospective cross-sectional, 8.33% prospective open label study, 8.33% intervention study and 8.33% study called masked trial. Although studies evaluate the technique of eye drop instillation, only 8.33% describe in the article the reference in the literature used to evaluate patients. 50% of articles acknowledged some sort of bias or limitation. Conclusion： The limitations inherent in these types of studies should guide future research.

The clinical use of interventional chemotherapy and intravesical instillation for preventing recurrence of superficial bladder cancer

Objective To study the therapeutic efficacy of combined interventional chemotherapy and intravesical instillation of mitomycin on preventing bladder cancers from recurring after local ablation. Methods 28 patients with superficial bladder cancers were randomized into combined interventional chemotherapy and intravesical instillation of mitomycin or intravesical instillation of mitomycin alone for preventing recurrence after local ablation. The result was assessed by x2 test. Results The patients have been followed up for 12-26 months (mean 21 months). 1 case has had tumor recurrence in the combined modality therapy group and 4 in the intravesical instillation alone group, the tumor recurrence rate being 7% (1/14) and 29% (4/14) respectively (P【0.05). Conclusion Combined use of interventional chemotherapy and intravesical instillation of mitomycin is effective in preventing superficial bladder cancer from recurring after local ablation with fewer adverse effects. The ragimen is not only reliable but

Swallowing Difficulties,Oral Symptoms,and Nutrition in Long-Term Care Elderly Residents-A Secondary Publication

Oral health is often impaired in people living in residential care.In older people,poor oral health is associated with functional deficits,multiple sclerosis,and memory disorders.Keeping one’s teeth healthy throughout life would promote both oral health and general health.Biting and swallowing problems in older people are also linked to oral health,limiting eating activities and requiring diet changes to softer foods that are easy to chew and swallow.This may limit dietary diversity and adequate nutrient intake.Although eating-related chewing and swallowing problems are common in institutionalized residents,they are often addressed too late,when the resident is already malnourished.Nutrition in nursing and retirement homes has been the subject of various studies since the 2000s.However,studies on swallowing and chewing difficulties are scarce and their link to adequate nutrient intake has received lesser attention[6,7].

Pilot study of intravesical instillation of two new generation anthracycline antibiotics in prevention of superficial bladder cancer recurrence

Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in the bladder are observed in some patients. There are numerous reports of trials of intravesical instillation of anticancer agents with the objective of lowering this recurrence rate. The aim of this study was to compare the prophylactic efficacy and safety of epirubicin （EPI）, pirarubicin （THP） and hydroxycamptothecin （HCPT） in superficial bladder cancer.Methods This study enrolled a total of 189 patients who had been diagnosed with superficial bladder cancer during the period from 2004 through 2007 at Beijing Friendship Hospital. All patients were randomly allocated to one of three treatment groups. Patients in group A received 29 doses of EPI 30 mg/30 ml, patients in group B received 29 doses of THP 30 mg/30 ml, and patients in group C received 29 doses of HCPT 30 mg/30 ml, over a period of 24 months.Results The recurrence-free rate in the 2 anthracycline treatment groups （A and B） were significantly better than that of the HCPT treatment group. In the safety evaluation, the incidences of pollakiuria, pain on urination, dysuria, hematuria,and contracted bladder were not significantly different between groups A and B, but some were significantly higher in groups A and B than that in group C.Conclusion The efficacy of EPI and THP was significantly better than HCPT in the prevention of bladder cancer recurrence.

Efficacy of immediate instillation combined with regular instillations of pirarubicin for Ta and T1 transitional cell bladder cancer after transurethral resection： a prospective, randomized, multicenter study

Background Immediate intravesical instillation of chemotherapeutic agents after transurethral resection （TUR） of non- muscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin （THP~） as prophylaxis compared to regular instillations only after TUR operation. Methods This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer （Ta and T1） pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP~ once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only. Results A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group （14.3%; P=0.042）. Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group （6.8%） than in the control group （14.0%; P=0.047）, although no significant differences were found in high-risk patients. Conclusion One immediate dose of THP 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.

Neurotoxicity and brain localization of europium doped Gd2O3 nanotubes in rats after intranasal instillation

Europium doped Gd2O3nanotubes(Gd2O3:Eu3+NTs) were synthesized and characterized. Then,the neurotoxicity and brain localization of Gd2O3:Eu3+NTs were evaluated. All experimental rats were administered by intranasal instillation with 30 μL Gd2O3:Eu3+NTs suspension 3.0 and 15.0 mg/mL respectively every other day for 35 consecutive days, and the rats of control group were administered with an equal volume of physiological saline. The Morris water maze was used to assess the rats’ spatial learning and memory ability. The oxidative stress-related biomarkers and the activity of AChE in striatum and hippocampus were analyzed, and the histopathology of hippocampus and striatum was observed.The brain localization of gadolinium(Gd) was measured. The results showed that the escape latency of the rats in high-dose group prolonged significantly compared with that of control group after treatment of six weeks(p < 0.05), and the swimming time in D quadrant of high-dose group shortened significantly compared with the control group(p < 0.01). In addition, high-dose Gd2O3:Eu3+NTs could decrease the activity of GSH-Px and CAT in hippocampus and the activity of SOD in striatum(p < 0.05). MDA content in hippocampus and striatum of high-dose group increased(p < 0.05). High dose Gd2O3:Eu3+NTs could increase the activity of AChE in hippocampus(p < 0.05) and in striatum(p < 0.001). But there were no significant differences between the low-dose group and control group(p > 0.05). The results of Gd localization in brain showed that the ranking of Gd levels was olfactory bulb > striatum > hippocampus> cerebellum > brain stem > frontal cortex. The pathology results indicated that high dose Gd2O3:Eu3+NTs resulted in degeneration necrosis, nucleus pycnosis, and axons disappearance of the nerve cells at CA1, CA3 and DG area of hippocampus. Therefore, the results implied that Gd2O3:Eu3+NTs have the potential neurotoxicity and a possible danger in causing neurodegenerative disorders after intranasal instillation.

INTRAVESICAL INSTILLATION OF INTERLEUKIN-2 AN EFFECTIVE METHOD FOR PREVENTING THE RECURRENCE OF BLADDER CANCER

The result of intravesical instillation with interleukin-2 (IL-2) for preventing the recurrence of bladder cancer and discussion of its mechanism was reported. 20 patients with histologically confirmed bladder transitional cell carcinoma were investigated. 2 000 u IL 2 was intravesically instillated every day for six days after resection of the neoplasm. The serum level of tumor necrosis factor (TNF) was significantly increased in 17 patients after IL-2 therapy. Recurrence occurred in 4 patients during the follow-up period of 10-18 months. The basic level of serum TNF was low and was not increased or even decreased after IL-2 in these patients. On the contrary, recurrence did not occur in another 5 patients with low basic level of TNF, but it was significantly increased after treatment of IL-2. TNF played a key role in preventing the recurrence of bladder cancer. The patients who had low basic level of TNF, which did not markedly increase or even decrease after IL-2 therapy were at high risk of recurrenc

Negative pressure wound therapy with instillation:effects on healing of category 4 pressure ulcers

Aim: The use of negative pressure wound therapy (NPWT) is well established in the treatment of chronic wounds. NPWT with instillation (NPWTi) combines traditional NPWT with the application of a topical irrigation solution (in this case octenidine based octenilin? wound irrigation solution) within the wound bed. The purpose of the study was to investigate the impact of NPWTi on pressure ulcers (PUs). Methods: In total 13 patients with PUs in different locations were treated with negative pressure therapy combined with ocitenidine based instillation fluid after first surgical debridement. After 6 days the dressing was removed and wound closure using different local flaps was performed. Results: Normal wound healing without irritation was found 30 days post-debridement and after 90 days the wounds showed complete healing. No adverse incidents occurred and no toxic tissue reactions were documented. During the follow up period, there was no recurrence of the PU in any of the treated patients. Conclusion: It is generally recognised that for chronic wounds to heal, optimum wound bed preparation is of paramount importance. This helps prepare for secondary healing, skin grafting or coverage with flaps. Tests were performed in vitro simulating real clinical conditions using PU vacuum exudates. These tests quantified the antiseptic efficacy of octenilin? wound irrigation solution in the eradication of microorganisms. Further research is needed to establish the role of NPWTi with octenilin? in the management of category 4 PUs, but these initial results on 13 patients lead in the direction of developing an enhanced protocol for the treatment of chronic wounds.

Utilizing Instilling Negative Pressure Wound Therapy with Vashe Wound Solution for an Infected Sternal Dehiscence: A Case Report

Utilization of negative pressure wound therapy with instillation (NPWTi) for sternal dehiscence wounds secondary to sternal wound infection after surgery has become an accepted therapy. NPWTi accelerates wound healing through macrostrain, microstrain, and cyclic fluid instillation. Wounds benefit from additional superficial infection control with the removal of microorganisms, the release of proinflammatory mediators, stimulation of angiogenesis, as well as mechanical debridement. However, very few cases of utilizing NPWTi in the treatment of sternal wound infections have been reported in the literature. This case study describes the use of NPWTi with hypochlorous acid for the treatment of a sternal wound infection.

Sudden sensorineural hearing loss-A contemporary review of management issues

Sudden sensorineural hearing loss(SSNHL)is an enigmatic entity,with obscure pathophysiology and debatable efficacy of the treatment agents used.An underlying cause is identified in only 10-15%of cases.The management of the remaining patients,classified as‘idiopathic’,is empirical,and is conventionally with systemic steroids,vasodilator therapy,rheological agents,and antioxidants,to list a few amongst the host of the agents employed for the treatment.The availability of conflicting outcomes and lack of conclusive evidence has resulted in the propagation of consensus-based treatment protocols.In the present review,we discuss the various controversial issues and newer developments in the management of idiopathic SSNHL.The current review aims to present a narrative outlook of the updated evidence base available from PUBMED,augmented with relevant designated publications.

Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis

AIM: To assess the efficacy of topical Semaphorin 3A(SEMA3A) in the treatment of allergic conjunctivitis.METHODS: Experimental allergic conjunctivitis(EAC)mice model induced by short ragweed pollen(SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin(H&E) staining, immunofluor-escence and light microscope photographs. Early phase took the samples in 24 h after instillation and late phase took the samples between 4 to 14 d after the start of treatment. The study use of topical SEMA3A(10 U, 100 U,1000 U) eye drops and subconjunctival injection of SEMA3 A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.· RESULTS: Clinical score of composite ocular symptoms of the mice treated with SEMA3 A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3 A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3 A 1000 U-treated group were significantly lower than low-concentration of SEMA3 A treated groups and non-treated group. SEMA3 A treatment also suppressed T-cell proliferation in vitro and decreased serum total Ig E levels in EAC mice. Moreover, treatment of SEMA3 A suppressed Th2-related cytokines(IL-5, IL-13 and IL-4)and pro-inflammatory cytokines(IFN-γ, IL-17 and TNF-α)release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice.CONCLUSION: SEMA3 A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3 A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.

Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM_(2.5)-treated Rats

Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase （GSH-Px） and concentration of malondialdehyde （MDA） were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length （μm） and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length （μm） and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length （μm） and rate of tail are simple and valuable biomarkers of PM2 5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device

Background: Middle East respiratory syndrome coronavirus(MERS-Co V), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health.Methods: To simulate the clinical aerosol transmission route, h DPP4 transgenic mice were infected with MERS-Co V by an animal nose-only exposure device and compared with instillation-inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues.Results: MERS-Co V aerosol-infected mice with an incubation period of 5-7 days showed weight loss on days 7-11, obvious lung lesions on day 7, high viral loads in the lungs on days 3-9 and in the brain on days 7-9, and 60% survival. MERS-Co V instillation-inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3-5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3-5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS-Co V aerosol-infected mice than in the MERS-Co V instillation-inoculated mice.Conclusion: h DPP4 transgenic mice were successfully infected with MERS-Co V aerosols via an animal nose-only exposure device, and aerosol-and instillation-infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS-Co V developed disease and lung pathology progressions that more closely resembled those observed in humans.

Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis

Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties.Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been investigated.This study aimed to explore the ability of ivermectin(0.6 mg/kg)to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model.This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF.The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury,as manifested by the reduced infiltration of inflammatory cells,as well as decreased the inflammation and fibrosis scores.Intriguingly,ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-β1(TGF-β1)and fibronectin protein expression,highlighting its anti-fibrotic activity.This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome,as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),with a subsequent decline in the interleukin-1β(IL-1β)level.In addition,ivermectin inhibited the expression of intracellular nuclear factor-κB(NF-κB)and hypoxia‑inducible factor‑1α(HIF-1α)proteins along with lowering the oxidative stress and apoptotic markers.Altogether,this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin.These beneficial effects were mediated,at least partly,via the downregulation of TGF-β1 and fibronectin,as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1αand NF-κB.

Transrectal ultrasonography-guided transperineal bilateral seminal vesicle puncture and continuous irrigation for the treatment of intractable hematospermia

Hematospermia is a rare condition, but often causes frustration. The reason for this frustration is that theexact incidence of hematospermia remains unknown and its cause is difficult to determine.^1 Many reports in the past decades have focused on the etiology of hematospermia.^2 Hematospermia is treated initially by administration of antibiotics, coagulants, and sex steroid hormones. However, some cases may prove resistant to this therapy and the condition may continue. For some intractable and agnogenic cases, the therapeutic strategy mentioned above is not very effective. Recently, we treated 63 such nonresponsive patients by direct continuous antibiotic irrigation into the bilateral seminal vesicles through puncture under transrectal ultrasonography （TRUS） guidance.