INFLUENCE OF PAPAVERINE AND COMMERCIAL DIETARY SUPPLEMENTS ON BLOOD GLUCOSE AND BODY WEIGHT IN OBESE DOGS.

Our experiments showed that papaverine inhibits sugar absorption in vivo as well as in vitro. Papaverine blocks the absorption of sugar both in healthy and diabetic animals. Oral administration of papaverine significantly reduced blood sugar level but after an hour blood sugar level showed tendency to come back to the initial levels that were characteristic for these diabetic dogs. Dietary supplement made of herbal remedies and papaverine has proven to be quite effective in reducing body weight in dogs. For a month, dogs with initial overweight lost on average more than 1 kg (10+%), that is a very good result for their size.

Intraarterial papaverine for relief of catheter-induced peripheral arterial vasospasm during pediatric cardiac surgery: A randomized double-blind controlled trial.

BACKGROUND: Maintaining the patency of peripheral arterial lines in pediatric patients during surgery can be challenging due to multiple factors, and catheter-related arterial vasospasm is a potentially modifiable cause. Papaverine, a potent vasodilator, improves arterial line patency when used as a continuous infusion in the pediatric intensive care setting, but this method is not convenient during surgery. AIM: Extrapolating from the benefit seen in the intensive care unit, the authors hypothesize that a small-volume intraarterial bolus of papaverine immediately after arterial line placement will reduce vasospasm-related arterial line malfunction. METHODS: This was a prospective, randomized, double-blind study. Patients less than 17 years of age undergoing cardiac surgery were enrolled. Patients were randomized into the heparin or papaverine groups. Immediately after arterial line insertion, an intraarterial bolus of heparin (2 units/ml, 1 ml) or papaverine (0.12 mg/ml, 1 ml) was administered (T1, Figure 1). An optimal waveform was defined as the ease of aspirating a standardized blood sample within 30 s, absence of cavitation when sampling, absence of color change at the catheter site during injection, and presence of a dicrotic notch. The primary outcome evaluated was the presence of an optimal arterial waveform at 5 min after the first randomized dose (T1 + 5 min). The secondary outcomes were the presence of optimal arterial waveform an hour after the first dose and the ability of papaverine to rescue suboptimal waveforms. RESULTS: A total of 100 patients were enrolled in the study. Twelve patients were excluded from the analysis. Complete datasets after randomization were available in 88 patients (heparin group, n = 46; papaverine group, n = 42). At baseline, groups were similar for age, weight, arterial vessel size, and arterial line patency. At T1 + 5 min, an improvement in the waveform characteristics was observed in the papaverine group (heparin,39% [8/46] vs. papaverine, 64% [27/42]; p = .02; odds ratio, 2.8; 95% CI, 1.2 to 6.6, Figure 3, Table 2). At the end of 1 h, both groups showed continued improvement in arterial line patency. After the second dose, a higher number of patients in the heparin group had suboptimal waveforms and were treated with papaverine (heparin,37% [17/46] vs. papaverine,17% [7/42], p = .05). Patients in the heparin group treated with papaverine showed significant improvement in patency (13/17 vs. 3/7, p = .01). No serious adverse events were reported. CONCLUSIONS: In pediatric patients, papaverine injection immediately after peripheral arterial catheter placement was associated with relief of vasospasm and improved initial arterial line patency. Further, papaverine can be used as a rescue to improve and maintain arterial line patency.

Papaverine, a promising therapeutic agent for the treatment of COVID-19 patients with underlying cardiovascular diseases (CVDs).

The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis-dependent manner. Because ACE2 is highly expressed in the heart, SARS-CoV-2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system during COVID-19 treatment. Papaverine is a unique vasodilator alkaloid that is clinically used in the treatment of vasospasm. Interestingly, this compound has potent and direct effects on a wide range of viruses, and could also prevent viral exploitation mechanisms of the host cell facilities by inhibiting some cellular signaling pathways such as p38 MAPK. This pathway was recently introduced as a promising target for the treatment of COVID-19. Papaverine also has anti-inflammatory effects which is useful in combating the hyper-inflammatory phase of the COVID-19. Unlike some medications that have severe dosage-restrictions in the treatment of COVID-19 due to cardiac side effects, papaverine is recommended for use in many heart disorders. The ability of papaverine to treat COVID-19 has become more promising when the results of some extensive screenings showed the strong ability of this compound to inhibit the cytopathic effects of SARS-CoV-2 with EC50 of 1.1 µM. Having several therapeutic effects along with desired safety profile raises this hypothesis that papaverine could be a promising compound for the suppression of SARS-CoV-2 and prevention of ischemia/vasoconstriction-related complications in COVID-19 disease, especially in patients with underlying cardiovascular diseases (CVDs).

The Influence of Oral Drotaverine Administration on Materno-Fetal Circulation during the Second and Third Trimester of Pregnancy.

Background and Objectives: The study aimed to evaluate the effect of the oral administration of drotaverine on maternal and fetal circulation as measured by Doppler sonography in women with a risk of preterm birth. Materials and Methods: The present prospective study was conducted on 34 women with singleton pregnancy at 26-36 weeks of gestation. Doppler flow and pulsatility index (PI) assessments of the umbilical artery, fetal middle cerebral artery, and uterine arteries were performed before and 90-120 min after oral drotaverine administration. Results: There were no statistically significant differences between the Doppler assessment (PI Uma-umbilical artery, MCA-middle cerebral artery, and ltUta-left uterine artery) before drotaverine administration and 90-120 min after oral intake, but there were statistically significant differences between the PI assessment of the rtUta (right uterine artery, 0.55 vs. 0.75, p = 0.05) and the mean of the Uta (0.66 vs. 0.74, p = 0.03). For changes in the CUR (cerebro-umbilical ratio) and % changes in the CUR and mean PI of the Uta, there was no correlation with obstetric history, AFI (amniotic fluid index), gestation week, infertility history, systolic pressure, or diastolic pressure. There was a statistically positive correlation between changes in the CUR and % change in the CUR and body weight and in height. Conclusions: Drotaverine has no statistically significant influence on the MCA and Uma PI. The oral administration of drotaverine has an impact on PI rtUta and the mean PI Uta.

Antinociceptive activity of the novel RAGE inhibitor, papaverine, in a mouse model of chronic inflammatory pain.

Extracellular high-mobility group box 1 (HMGB1) is known to mediate the inflammatory response through pattern recognition receptors, including the receptor for advanced glycation end products (RAGE) or the toll-like receptors (TLRs). The aim of the present study was to investigate whether papaverine, a novel RAGE inhibitor, could suppress inflammatory pain in mice after several time points, which was induced by the injection of complete Freund's adjuvant (CFA). We also investigated the influence of redox modulation during a state of chronic inflammatory pain. Although papaverine did not suppress CFA-induced mechanical allodynia on Day 7, papaverine significantly suppressed CFA-induced mechanical allodynia on Days 14 and 28. In contrast, the radical scavenger N-tert-Butyl-α-phenylnitrone (PBN) suppressed mechanical allodynia in mice on Days 7 and 14, but not on Day 28. We demonstrated that the RAGE inhibitor improves mechanical allodynia in chronic inflammatory conditions. Moreover, we also found that high levels of reactive oxygen species (ROS) contributed to the early phase of CFA-induced mechanical allodynia. Precisely, lower ROS levels contributed to the inflammatory pain response via the all-thiol HMGB1/RAGE signaling pathway during the chronic state. These findings led us to propose that ROS levels modulate RAGE and/or TLR4-mediated inflammatory allodynia by regulating the concentrations of disulfide HMGB1 or all-thiol HMGB1.

Drotaverine Inhibitor of PDE4: Reverses the Streptozotocin Induced Alzheimer's Disease in Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with decline in memory and cognitive impairments. Phosphodiesterase IV (PDE4) protein, an intracellular cAMP levels regulator, when inhibited act as potent neuroprotective agents by virtue of ceasing the activity of Pro-inflammatory mediators. The complexity of AD etiology has ever since compelled the researchers to discover multifunctional compounds to combat the AD and neurodegeneration. The aim of this study was to probe into role of drotaverine a PDE4 inhibitor in the management of AD. Albino mice were divided into seven groups (n = 10). Group 1 control group received carboxy methyl cellulose (CMC 1 mL/kg), group II diseased group treated with streptozotocin (STZ 3 mg/kg) by intracerebroventricular (ICV) route, group III administered standard drug Piracetam 200 mg/kg and groups IV-VII were given drotaverine (10, 20, 40, and 80 mg/kg i/p respectively). Groups II-VII were given STZ (3 mg/kg, ICV) on 1st and 3rd day of treatment to induce AD. All the groups were given their respective treatments for 23 days. Improvement in learning and memory was evaluated by using behavioral tests like open field test, elevated plus maze test, Morris water maze test and passive avoidance test. Furthermore, brain levels of biochemical markers of oxidative stress, neurotransmitters, ß-amyloid and tau protein were also measured. Drotaverine showed statistically significant dose dependent improvement in behavioral and biochemical markers of AD: the maximum response was achieved at a dose level of 80 mg/kg. The Study concluded that drotaverine ameliorates cognitive impairment and as well as exhibited modulated the brain levels of neurotransmitters.

Clinical Efficacy of Intracoronary Papaverine After Nicorandil Administration for Safe and Optimal Fractional Flow Reserve Measurement.

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

Pluripotent anti-inflammatory immunomodulatory effects of papaverine against cerebral ischemic-reperfusion injury.

The mechanism of the papaverine (PV) for the treatment of cerebral ischemia remains unclear. A total of 42 mice induced with focal cerebral ischemia were randomly divided into three groups: PV,baicalin (BA)and vehicle group. Both PV and BA could significantly reduce the ischemic infarct volume (P < 0.05). Pathway enrichment analysis was performed on MetaCore™ to search the molecular pathways associated with the gene expression profile of PV, compared with vehicle and BA. Compared with vehicle, we found that 60% of the top 10 pathways in PV group were related to immune response. The top 10 biological processes of the targeted pathways were mainly related to the multiple immunomodulatory process of neuro-vascular inflammation, including immune_Th17-deried cytokins, regulation of angiogenesis, cell adhesion_Leucocyte chemotaxis, antigen presentation, cell adhesion_synaptic contact, and inflammation related to Amphoterin signaling. Moreover, compared with BA, 17 pathways of PV were identified, and 58.82% (10/17) were also related to immune response, especially, half of the top 10 pathways with the lower p-value. In these top 10 pathways, 4 were the cytokine-mediated signaling pathways, which play key role in inflammation, like IL-17 signaling pathways with the activation of G-CSF,IL-23,RANKL, p38MAPK and NF-κB.These findings indicate that PV may be an efficacious pluripotent anti-inflammatory agent against cerebral ischemic-reperfusion injury by targeting on multiple immunomodulatory process of neuro-vascular inflammation.

Papaverine identified as an inhibitor of high mobility group box 1/receptor for advanced glycation end-products interaction suppresses high mobility group box 1-mediated inflammatory responses.

The interaction of high mobility group box 1 (HMGB1), which is secreted from immune and dying cells during cellular infection and injury, and receptor for advanced glycation end-products (RAGE) appears to be critical for acute and chronic inflammatory disorders. Here we designed a unique cyclic ß-hairpin peptide (Pepb2), which mimics the predicted RAGE-binding domain of HMGB1. Pepb2 competitively inhibited HMGB1/RAGE interaction. We then identified papaverine as a Pepb2 mimetic by in silico 3D-structural similarity screening from the DrugBank library. Papaverine was found to directly inhibit HMGB1/RAGE interaction. It also suppressed the HMGB1-mediated production of pro-inflammatory cytokines, IL-6 and TNF-α, in mouse macrophage-like RAW264.7 cells and bone marrow-derived macrophages. In addition, papaverine attenuated mortality in cecal ligation puncture-induced sepsis model mice. Taken together, these findings indicate that papaverine could become a useful therapeutic against HMGB1/RAGE-mediated sepsis and other inflammatory diseases.

The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson's disease mouse models.

BACKGROUND: Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Thus, the development of agents that can control neuroinflammation has been suggested as a promising therapeutic strategy for PD. In the present study, we investigated whether the phosphodiesterase (PDE) 10 inhibitor has anti-inflammatory and neuroprotective effects in neuroinflammation and PD mouse models. METHODS: Papaverine (PAP) was utilized as a selective inhibitor of PDE10. The effects of PAP on the expression of pro-inflammatory molecules were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells by ELISA, RT-PCR, and Western blot analysis. The effects of PAP on transcription factors were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, and Western blot analysis. Microglial activation and the expression of proinflammatory molecules were measured in the LPS- or MPTP-injected mouse brains by immunohistochemistry and RT-PCR analysis. The effect of PAP on dopaminergic neuronal cell death and neurotrophic factors were determined by immunohistochemistry and Western blot analysis. To assess mouse locomotor activity, rotarod and pole tests were performed in MPTP-injected mice. RESULTS: PAP inhibited the production of nitric oxide and proinflammatory cytokines in LPS-stimulated microglia by modulating various inflammatory signals. In addition, PAP elevated intracellular cAMP levels and CREB phosphorylation. Treatment with H89, a PKA inhibitor, reversed the anti-inflammatory effects of PAP, suggesting the critical role of PKA signaling in the anti-inflammatory effects of PAP. We verified the anti-inflammatory effects of PAP in the brains of mice with LPS-induced systemic inflammation. PAP suppressed microglial activation and proinflammatory gene expression in the brains of these mice, and these effects were reversed by H89 treatment. We further examined the effects of PAP on MPTP-injected PD model mice. MPTP-induced dopaminergic neuronal cell death and impaired locomotor activity were recovered by PAP. In addition, PAP suppressed microglial activation and proinflammatory mediators in the brains of MPTP-injected mice. CONCLUSIONS: PAP has strong anti-inflammatory and neuroprotective effects and thus may be a potential candidate for treating neuroinflammatory disorders such as PD.

The protective effect of Papaverine and Alprostadil in rat testes after ischemia and reperfusion injury.

OBJECTIVE: To investigate the effect of papaverine and alprostadil on testicular torsion-detorsion injury in rats. MATERIALS AND METHODS: A total of 40 male Wistar-Albino rats were used in this study. Four hours of right testicular torsion was applied to each group, excluding sham operated group. The torsion-detorsion (T/D), T/D + papaverine and T/D + alprostadil groups received saline, papaverine and alprostadil at the same time as surgical detorsion, respectively. At 14 days after the surgical detorsion, ischaemic changes and the degree of damage were evaluated with Cosentino scoring and the Johnson tubular biopsy score (JTBS). RESULTS: JTBS was determined as 8.8±2.7 in the Sham group, 5.08±1.9 in the T/ D+papaverine group, 5.29±2.3 in the T/D +alprostadil group and 2.86±1.9 in the TD group. The JTBS was determined to be statistically significantly high in both the T/D + papaverine group and the T/D + alprostadil group compared to the T/D group (p=0.01, p=0.009). In the T/D + papaverine group, 3 (43 %) testes were classified as Cosentino 2, 3 (43%) as Cosentino 3 and 1 (14 %) as Cosentino 4. In the T/D +alprostadil group, 5 (50 %) testes were classified as Cosentino 2, 3 (30 %) as Cosentino 3 and 2 (20%) as Cosentino 4. CONCLUSION: The present study indicated that spermatic cord administration of alprostadil and papaverine showed a protective effect against ischemia/reperfusion injury after right-side testes torsion and histological changes were decreased after testicular ischemia reperfusion injury.

Evaluation of Ophthalmic Artery Branch Retrograde Intervention in the Treatment of Central Retinal Artery Occlusion (CRAO).

BACKGROUND Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)-guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. MATERIAL AND METHODS Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. RESULTS No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ²=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ²=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ²=0.25, P=0.88). CONCLUSIONS The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach.

[COMPLEX TREATMENT OF PURULENT-NECROTIC COMPLICATIONS IN THE PATIENTS, SUFFERING DIABETIC FOOT SYNDROME, USING NEGATIVE TRESSURE AND CAPICOR PREPARATION].

The comparative analysis data were presented, concerning the results of complex treatment of 28 patients, suffering ischemic-gangrenous form of the diabetic foot syndrome, developing on background of chronic ischemia of the lower extremities stage IV. In 14 patients (main group) a routine complex of the treatment measures was added by application of an active pressure (negative pressure wound therapy - NPWT) and a capicor preparation; 14 patients (the comparison group) were treated in accordance to routine scheme. In accordance to the comparative analysis data, in patients of the main group the wound surface sarea have kept reducing in twice more rapid, than in a comparison group, the wounds healing was achieved in 94% patients, duration of the patients' stationary stay have reduced by (5.2 ± 1.4) days.

Penile vascular diagnostic categorization using penile duplex Doppler ultrasound: Differences in vascular hemodynamics parameters by differences in anatomic sampling location.

OBJECTIVES: In 2013 the International Society for Sexual Medicine(ISSM) published the guidelines regarding the standard operating procedure (SOP) for penile duplex Doppler ultrasound (PDDU). Although ISSM-SOP have given important strides in reducing interobserver variability in PDDU by procedural protocol and parameters these guidelines do not address the anatomic location along the penis at which hemodynamic measurements have to be done. In our opinion a "double sampling" may be interesting to detect the arteriogenic or venogenic nature of the erectile dysfunction (ED). In particular sampling measurements at the "crus" (at the level of the peno-scrotal junction) may be significative for detection of veno-occlusive dysfunction (VOD),whereas an evaluation at "mid penis" (1/2 distance between peno-scrotal junction and coronal sulcus), may be useful to diagnose an arterial insufficiency (AI). MATERIAL AND METHODS: We evalued 90 men, mean age 56.3, affected with ED of medium degree, responder to PDE5-I that urdergone to PDDU and also responder after pharmacologic intracavernosal injection (PII)of prostaglandin E1 20 mcg, with rigid erection and normal maintenance. We moreover evalued 90 men in youthful age (mean 35.2), in absence of vascular risk factors, no responder to PDE5-I that undergone to PDDU by PII at high dosage (bimix: prostaglandin E1 20 mcg, papaverine 20 mg). RESULTS: In the first pool the sampling at "mid penis" resulted significative for arterial insuffciency (AI) in 81% (73), in presence of normal or borderline end diastolic velocity (EDV). Sampling at the "crus" resulted negative for VOD in 90% (81). In the second pool, 66.6% (60) resulted responder with rigid erection and normal maintenance in presence of normal hemodynamic parameters: peak systolic velocity (PSV) and end diastolic velocity (EDV) both at the "crus" and at "mid penis" sampling. 33.4% (30) responded with a semirigid erection and manifested a constant deficit of maintenance; at the "crus"and at "mid penis" the hemodynamic arterial parameters resulted normal. At the "crus" the EDV resulted significantly augmented (VOD index) in 96.6% (29); at "mid penis" augmented EDV was founded in 50% (15). CONCLUSIONS: These observational data would be able to confirm the utility of a routinary "double sampling" procedure, at the "crus" and at "md penis", during PDDU in order to better distinguish between VOD or AI or in any case to be useful to stimulate a future more precise standardization in execution of PDDU examination.

Papaverine improves sublingual blood flow in patients with septic shock.

BACKGROUND: In recent years, microcirculatory blood flow alterations have been recognized to be stronger predictors of septic shock treatment outcomes than global hemodynamic variables. METHODS: In our self-controlled, interventional pilot clinical trial study, we investigated the effects of a single papaverine injection on the microcirculation in sepsis patients undergoing fluid resuscitation combined with vasopressor treatments. Fourteen septic shock patients admitted to the Peking University Third Hospital were included in the study, and each patient received 30 mg papaverine, which is the approximate dosage used to treat a conventional arterial spasm. Papaverine was administered as an intravenous bolus injection after systemic hemodynamic stabilization had been achieved by means of fluid resuscitation combined with dopamine and/or norepinephrine vasopressor medication. Baseline characteristics, as well as global hemodynamic and blood gas parameters, before and 60 min after papaverine injection were recorded and sublingual microcirculatory data at baseline and 15, 30, and 60 min after papaverine administration obtained using sidestream dark-field video microscopy. RESULTS: The perfused vessel density of small vessels was significantly increased 30 and 60 min after papaverine administration (P < 0.01), and the proportion of perfused small vessels (PPV), as well as the microvascular flow index, was significantly increased 30 min after papaverine (P < 0.05). There were no visible systemic effects, arrhythmia, or hypotension during the observation period in each patient. CONCLUSIONS: In our pilot study, papaverine transiently improved sublingual microcirculatory blood flow without influencing systemic hemodynamics in patients with septic shock, who required vasoconstrictors to maintain blood pressure during fluid resuscitation.

Intra-arterial administration of papaverine during mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: The use of stent retrievers for mechanical thrombectomy in acute ischemic stroke may induce significant vasospasm, which at the early phases of reperfusion may be crucial for rethrombosis of the recanalized vessel. We aimed to study whether the use of intra-arterial papaverine in selected cases of vasospasm was associated with improved cerebral perfusion, arterial reocclusion, or increased hemorrhagic complications. METHODS: We retrospectively studied 9 consecutive patients with large artery acute occlusion, treated with stent retriever and intra-arterial papaverine. Onset to administration of intravenous recombinant tissue-plasminogen activator time, baseline National Institute of Health Stroke Scale, time to reperfusion, number of passes of the stent retriever, modified Rankin Scale score at discharge, postprocedural hemorrhage, onset to reperfusion time, papaverine dose, and thrombolysis in cerebral infarction grade were recorded in all patients. RESULTS: After papaverine administration, the caliber of the infused arteries and their flow was increased in all cases. In none of the treated cases a reocclusion occurred after papaverine infusion. In one of the studied patients (11%), a parenchymal bleeding occurred 36 hours postoperatively. CONCLUSIONS: This small study suggests that intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after mechanical thrombectomy in acute ischemic stroke is effective and safe.

[APPLICATION OF LARGE SUBCUTANEOUS VEIN AS MATERIAL FOR DISTAL SHUNTING IN CRITICAL ISCHEMIA OF THE LOWER EXTREMITY TISSUES].

While performing autologous reconstruction of distal arteries in 24 patients in chronic critical ischemia of the lower extremity tissues the method of a large subcutaneous vein mobilization, using a ring-like desobliterator,was applied. This have permitted to reduce the procedure traumaticity, comparing with a standard method. Additional application of pharmacological vasodilatation of venous transplant have permitted to avoid the risk, connected with impact of hydraulic vasodilatation on the venous wall functional state.

Effectiveness of papaverine cisternal irrigation for cerebral vasospasm after aneurysmal subarachnoid hemorrhage and measurement of biomarkers.

Cisternal irrigation with thrombolytic agents was used to prevent post-SAH vasospasm, but its role remained inconclusive. To verify effectiveness of papaverine (PPV) in preventing vasospasm, we studied relationship between inflammatory biologic markers and vasospasm. This prospective study included 121 patients with clipped anterior circulation aneurysms that had ruptured, and 372 control patients. Patients were divided into three groups according to cisternal irrigation method: simple drain, papaverine group, and urokinase (UK) group. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in CSF and serum on days 3 and 7 after SAH. The PPV group showed similar incidence of vasospasm with UK group, but lower incidence than the simple drain group. The levels of ICAM-1 and VCAM-1 were significantly higher in the SAH group than in the control group. CSF and serum levels were more elevated on day 7 than day 3, and the degree of elevation were more marked when measured in the CSF than in the serum. However, there was no statistical difference between measured levels of ICAM-1 and VCAM-1, and vasospasm development. PPV cisternal irrigation was similarly effective as UK at preventing vasospasm. Although neither PPV nor UK irrigation could reduce the concentration of adhesion molecules compared with simple drain, we found levels of ICAM-1 and VCAM-1 were specifically elevated in the CSF. Therefore, further research should focus on anti-inflammation as a therapeutic target against cerebral vasospasm and on the CSF as the optimum place where such inflammatory action practically brought about.

[Efficiency of etiologic correction of concomitant ascaridosis in the complex treatment of chronic pancreatitis].

The of antihelmintic preparation albendazole using in the complex treatment of patients with chronic pancreatitis with the concomitant ascaridosis was promote regression of clinical demonstration of basic and concomitant diseases (P < 0.05). Options of coprogram and the structural state of pancreas from data of ultrasonography in marks by Marseille-Cambridge classification of chronic pancreatitis, after the conducted treatment became the better (P < 0.05), that established expedience of the use of albendazole in complex treatment of patients with a chronic pancreatitis with a concomitant ascaridosis.

A comprehensive history of injection therapy for erectile dysfunction, 1982-2023.

INTRODUCTION: Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982. OBJECTIVES: To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy. METHODS: Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed. RESULTS: The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine. CONCLUSIONS: After 40 years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.