Cytotoxic effects of kinetin riboside and its selected analogues on cancer cell lines.

N6-[(Furan-2-yl)methyl]adenosine (kinetin riboside) and its seven synthesized analogues were examined for the ability to inhibit the growth of five human carcinoma cell lines and for comparison of normal human lung fibroblast cell line (MRC-5). Out of the compounds evaluated, 8-azakinetin riboside was shown to exhibit significant cytotoxic activity for 72 h treatment against ovarian OVCAR-3 and pancreatic MIA PaCa-2 cancer cells (IC50 = 1.1 µM) with an observed weaker effect against MRC-5 cells (IC50 = 4.6 µM). Kinetin riboside, as well as its N6-[(furan-3-yl)methyl]- and N6-[(thien-2-yl)methyl]- counterparts, also exhibited cytotoxic activities at low micromolar levels but were non-selective over MRC-5 cells.

Embryological basis of polyorchidism including classification, reproductive potential, and risk of malignancy: A review.

Polyorchidism, a congenital malformation characterized by supernumerary testes (SNTs), is usually revealed incidentally during ultrasound or open scrotal surgery. In the approximately 200 cases so far published in the literature, the left side is affected more often than the right. Despite the rarity of this anomaly, a surgeon must have basic knowledge of its embryological basis and classifications to implement proper treatment and avoid overlooking it, since the consequences could harm the patient. This review summarizes previous classifications. It can be assumed that determining the risk of malignancy, and the level of reproductive potential based on location, vascularization, ductus deferens drainage, and environmental factors (e.g., temperature) affecting the SNTs, indicates the best approach to management. Therefore, we have created a new classification based on previous ones, addressing the aforementioned issues, which will guide the clinician to select the most appropriate treatment.

Impact of Internal Carotid Stenosis Treatment on Cerebral Blood Flow Volume: A Comparative Study between Preoperative and Postoperative Values.

BACKGROUND Among patients with ICA stenosis, there are some cases with elevated, undisrupted, and diminished cerebral blood flow (CBF). The aim of this study was to assess the influence of ICA stenosis treatment on postoperative CBF changes in relation to preoperative CBF values. MATERIAL AND METHODS We qualified 58 patients ≥65 years old (28 males, 30 females, mean age 71.02±6.34 years) for surgical intervention due to symptomatic ≥70% ICA stenosis. In all patients, a flow volume in all extracranial arteries (internal carotid [ICA], external carotid [ECA], and vertebral arteries [VA]) was measured preoperatively and 2-3 days following the surgery. The CBF values were compared with the ones established for a healthy population of the same age. RESULTS Preoperatively, there were 3 subgroups of patients, comparing to healthy population: with elevated CBF - "significant compensation," with undisrupted CBF - "mild compensation," and with diminished CBF - "no compensation." Postoperatively, a significant CBF increase was observed in patients with preoperative "no" and "mild compensation" - 277.18±154.26 ml/min (P=0.0000001) and 221.56±98.8 ml/min (P=0.0000001). In a "significant compensation" group, there was no flow increase observed (CBF change of 2.57±58.5 ml/min, P=0.954) - a redistribution of flow was observed. CONCLUSIONS In patients with lower preoperative CBF values, surgical treatment caused a significant increase in global cerebral inflow, which was more prominent in patients with the lowest preoperative CBF. In patients with high preoperative CBF, surgical treatment resulted in a flow redistribution, but did not cause a CBF increase. Volumetric flow assessment in DUS can predict hemodynamic benefit from surgery in terms of CBF increase.

Characteristics of Transfer RNA-Derived Fragments Expressed during Human Renal Cell Development: The Role of Dicer in tRF Biogenesis.

tRNA-derived fragments participate in the regulation of many processes, such as gene silencing, splicing and translation in many organisms, ranging from bacteria to humans. We were interested to know how tRF abundance changes during the different stages of renal cell development. The research model used here consisted of the following human renal cells: hESCs, HEK-293T, HK-2 and A-489 kidney tumor cells, which, together, mimic the different stages of kidney development. The characteristics of the most abundant tRFs, tRFGly(CCC), tRFVal(AAC) and tRFArg(CCU), were presented. It was found that these parental tRNAs present in cells are the source of many tRFs, thus increasing the pool of potential regulatory RNAs. Indeed, a bioinformatic analysis showed the possibility that tRFGly(CCC) and tRRFVal(AAC) could regulate the activity of a range of kidney proteins. Moreover, the distribution of tRFs and the efficiency of their expression is similar in adult and embryonic stem cells. During the formation of tRFs, HK-2 cells resemble A-498 cancer cells more than other cells. Additionally, we postulate the involvement of Dicer nuclease in the formation of tRF-5b in all the analyzed tRNAs. To confirm this, 293T NoDice cells, which in the absence of Dicer activity do not generate tRF-5b, were used.

Prevalence of obstructive sleep apnea in patients with peripheral arterial diseases.

BACKGROUND: The presence of obstructive sleep apnea (OSA), a novel cardiovascular risk factor, contributes to the development of peripheral arterial diseases (PAD). There is a lack of data showing how often these diseases coexist. AIMS: The aim of the study was to determine the prevalence of OSA in the population of patients with PAD. METHODS: Patients previously qualified for the first revascularization due to PAD were included in the study. All patients underwent an overnight sleep study to detect OSA. Diagnosis of OSA was made when the apnea-hypopnea index (AHI) was ≥5 per hour. RESULTS: From 141 patients (60% men, age 69.6 ± 9.5 years), OSA was diagnosed in 68 patients (48%). OSA occurred in mild form (5 ≤ AHI < 15/h) in 39 cases (28%), in moderate form (15 ≤ AHI < 30/h) in 21 cases (15%), and in severe form (AHI ≥ 30/h) in 8 cases (6%). Patients without OSA had significantly lower body mass index (BMI; 26.9 ± 5.5 vs. 27.7 ± 5.3 kg/m2, p = 0.01) and lower hip circumference (97.4 ± 11.7 vs. 98.7 ± 7.4, p = 0.04). There were no differences in the distribution of other investigated cardiovascular risk factors and diseases between these groups. There were no significant differences in OSA distribution or its severity between patients with lower extremity artery disease and carotid artery disease. CONCLUSIONS: The prevalence of OSA in patients with PAD is very high, affecting nearly half of the studied population.

Adrenal metastases - long-term results of surgical treatment, single-centre experience.

INTRODUCTION: The adrenal gland is a frequent site of metastases in different types of cancer. The aim of this study was to assess the results of metastatic adrenalectomy in a single institution and to identify factors for survival. MATERIAL AND METHODS: A retrospective, single-centre analysis of outcomes of 39 patients (22 male, 17 female) with adrenal metastases who underwent surgery within 14 years (2004-2017) was performed. The median age at the time of adrenal surgery was 64.8 years (range 49-79 years). RESULTS: In our study group non-small cell lung cancer (NSCLC) was the most frequent primary tumour type (15 pts), followed by renal cell carcinoma (RCC) (14 pts) and colon cancer (6 pts). Most of the metastases - 36 (92%) - were metachronous (> 6 months). All synchronous metastases were NSCLC. The mean time from primary cancer to adrenalectomy was 42.3 months (range 1-176) and was statistically longer for RCC. In 3 patients (8%) metastases were bilateral and both adrenal glands were removed. In all patients, surgery was limited to the adrenal gland, and no major complications of surgery were observed. The median overall survival after metastasectomy was 18 months (3-81) and was statistically longer for colon cancer - 29.5 months (p = 0.012). In patients who died, tumours were significantly bigger than in survivors, 76.5 mm vs. 52.5 mm (p = 0.026). CONCLUSIONS: Surgery for adrenal metastasis is safe and indications for this procedure should be individualized. In selected patients, surgical removal of adrenal metastasis was associated with longer survival.

Selective occlusion of splenic artery aneurysms with the coil packing technique: the impact of packing density on aneurysm reperfusion correlated between contrast-enhanced MR angiography and digital subtraction angiography.

PURPOSE: The aim was to evaluate the relationship between coil packing densities after splenic artery aneurysm (SAA) treatment using detachable microcoils and rates of SAA reperfusion and to suggest a post-treatment surveillance protocol using contrast-enhanced MRA. MATERIALS AND METHODS: Evaluated were 16 patients (4 men; mean age 46.7), who underwent true SAA embolization using detachable microcoils (Concerto, Medtronic). SAAs were treated by selective coil packing (CP) or stent-assisted coil exclusion (SAC). Contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA) were performed at 3 months post-procedure and correlated. RESULTS: Primary CP was used in 13 patients, while SAC was used in three patients. On follow-up, complete aneurysm occlusion was seen in seven patients (43.8%). Sac reperfusion occurred in nine patients (56.2%) and was demonstrated in all CE-MRA and six DSA studies. Mean aneurysm packing density was 20.10 ± 8.05% for the CP group and 32.90 ± 11.95% for the SAC group (p = 0.038). There was a significant difference in the incidence of aneurysm sac reperfusion on CE-MRA study between CP and SAC (9 vs. 0). No sac reperfusion was seen in aneurysms with packing densities ≥ 29%, irrespective of either embolization method. CONCLUSION: Favorable midterm results for coil packing of SAAs seem to depend on the coil packing density with a coil volume approximately a quarter of the aneurysm volume being most effective. Follow-up should involve the use of CE-MRA as this modality has been shown to be superior over DSA in detecting aneurysm reperfusion and coil compaction. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Acyclovir inhibits Cyprinid herpesvirus 3 multiplication in vitro.

Cyprinid herpesvirus 3 (CyHV-3), also known as koi herpesvirus (KHV), is an aetiological agent of a virulent and lethal disease in common and koi carp. In this study, we examined in vitro the anti-CyHV-3 activity of acyclovir (ACV), nucleoside analogue commonly used against human herpesviruses, as well as acyclovir monophospate (ACV-MP). The cytotoxicity of the ACV and the ACV-MP for two common carp cell lines, CCB (Common carp brain) and KF1 (Koi carp fin 1), was determined by means of MTT and crystal violet assays. In subsequent studies, the concentration of 66.67 µM was applied. The ACV and the ACV-MP (66.67 µM) inhibited a cytopathic effect (CPE) induced by the CyHV-3 virus in the CCB (ACV by 66%, ACV-MP by 58%) and the KF1 (ACV by 25%, ACV-MP by 37%). The viral load measured by the means of TaqMan qPCR was reduced in a range of 67%-93% depending on the analogue, the cell line and the time of incubation. The expression of viral genes (ORF149, ORF3, ORF134 and ORF78) in CCB cells infected with the CyHV-3 was strongly downregulated within the range of 78%-91%. In summary, both the ACV and the ACV-MP can inhibit CyHV-3 replication in vitro.

2-Aryl-8-aza-3-deazaadenosine analogues of 5'-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis.

A series of 5'-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3-triazolonucleoside with terminal alkynes and a Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent Ki values ranging from 6.1 to 25nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50µM.

HPLC and HPLC/MS/MS Studies on Stress, Accelerated and Intermediate Degradation Tests of Antivirally Active Tricyclic Analog of Acyclovir.

The degradation behavior of a tricyclic analog of acyclovir [6-(4-MeOPh)-TACV] was determined in accordance with International Conference on Harmonization guidelines for good clinical practice under different stress conditions (neutral hydrolysis, strong acid/base degradation, oxidative decomposition, photodegradation, and thermal degradation). Accelerated [40±2°C/75%±5% relative humidity (RH)] and intermediate (30±2°C/65%±5% RH) stability tests were also performed. For observation of the degradation of the tested compound the RP-HPLC was used, whereas for the analysis of its degradation products HPLC/MS/MS was used. Degradation of the tested substance allowed its classification as unstable in neutral environment, acidic/alkaline medium, and in the presence of oxidizing agent. The tested compound was also light sensitive and was classified as photolabile both in solution and in the solid phase. However, the observed photodegradation in the solid phase was at a much lower level than in the case of photodegradation in solution. The study showed that both air temperature and RH had no significant effect on the stability of the tested substance during storage for 1 month at 100°C (dry heat) as well as during accelerated and intermediate tests. Based on the HPLC/MS/MS analysis, it can be concluded that acyclovir was formed as a degradation product of 6-(4-MeOPh)-TACV.

Exploring the Survival Determinants in Recurrent Ovarian Cancer: The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Recurrent ovarian cancer (ROC) significantly challenges gynecological oncology due to its poor outcomes. This study assesses the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on ROC survival rates. MATERIALS AND METHODS: Conducted at the Medical University of Lublin from April 2011 to November 2022, this retrospective observational study involved 71 patients with histologically confirmed ROC who underwent CRS and subsequent HIPEC. RESULTS: The median overall survival (OS) was 41.1 months, with 3-year and 5-year survival rates post-treatment of 0.50 and 0.33, respectively. Patients undergoing radical surgery for primary ovarian cancer had a median OS of 61.9 months. The key survival-related factors included the Peritoneal Carcinomatosis Index (PCI) score, AGO score, platinum sensitivity, and ECOG status. CONCLUSIONS: The key factors enhancing ROC patients' survival include radical surgery, optimal performance status, platinum sensitivity, a positive AGO score, and a lower PCI. This study highlights the predictive value of the platinum resistance and AGO score in patient outcomes, underlining their role in treatment planning. Further prospective research is needed to confirm these results and improve patient selection for this treatment approach.

Bioactive Furanyl- or Thienyl-Substituted Nucleobases, Nucleosides and Their Analogues.

Five-membered heterocycles, including furan and thiophene, play a prominent role in drug design as structural units of bioactive molecules. This review is intended to demonstrate the importance of the furan-2-yl, furan-3-yl, thien-2-yl and thien-3-yl substituents in the medicinal chemistry of purine and pyrimidine nucleobases, nucleosides and selected analogues. Data presented in the article are limited to compounds containing heteroaromatic ring connected through a bond and not fused to other systems. The impact of bioisosteric replacement of aryl substituents with heteroaryl ones on activities was assessed by comparison of the title compounds with their aryl counterparts. A total of 135 heteroaryl-substituted and 35 aryl-substituted derivatives are mentioned in the text and shown in the figures. The following classes of compounds are included in the article: (i) 5-heteroaryl-2'-deoxyuridines and related compounds; (ii) 8-heteroaryl- 2,9-disubstituted adenine derivatives; (iii) O6-(heteroarylmethyl)guanines; (iv) 6-heteroaryl tricyclic guanine analogues; (v) 6-heteroaryl-9-benzylpurines and analogous compounds; (vi) N4- furfurylcytosine, N6-furfuryladenine, their derivatives and analogues; (vii) 6-heteroaryl purine and 7- deazapurine ribonucleosides; (viii) 7-heteroaryl-7-deazaadenosines, their derivatives and analogues; (ix) 4-heteroaryl fused 7-deazapurine nucleosides. In most cases various modifications of the lead compound structure performed in order to obtain the most favorable activity and selectivity are briefly discussed. The reviewed structure-activity relationship studies exemplify the search for compounds with optimized antiviral, antitumor, antimycobacterial or antiparkinsonian action.

Rapid Formation and Hybrid Treatment of a Large Superior Mesenteric Artery Aneurysm.

BACKGROUND Superior mesenteric artery (SMA) aneurysms account for about 5.5% of all visceral aneurysms, and are most commonly secondary to infectious causes or dissection. They tend to expand and rupture. Here, we present our successful diagnosis and treatment of a 41-year-old man with asymptomatic coeliac trunk stenosis, in whom the large aneurysm of the branch of the SMA developed in a very short time after conservative treatment of plastron appendicitis. CASE REPORT A 41-year-old man was diagnosed with plastron appendicitis during abdomen ultrasound (US) examination. Following 2 weeks of conservative treatment with intravenous antibiotic therapy, complete resolution of symptoms was obtained and confirmed in the computed tomography (CT) scan, and no other pathologies were diagnosed. Three weeks later, during the US examination, a 33-mm aneurysm of the branch of the SMA was diagnosed. The patient was admitted to the Vascular Surgery Department, where a critical stenosis of the coeliac trunk secondary to the compression by median arcuate ligament and a 33-mm true visceral aneurysm of one of the branches of the SMA were diagnosed. Successful treatment of the aneurysm was performed. Surgical decompression of the coeliac trunk and subsequent elective endovascular embolization of the SMA aneurysm with angioplasty of the coeliac trunk were performed. The postoperative period was uneventful and the patient was released from the hospital and remains asymptomatic. CONCLUSIONS Visceral artery aneurysm can form very quickly. In some of the aneurysms, a combination of open surgical and endovascular methods should be performed.

Risk of malignancy in adrenal tumors in patients with a history of cancer.

Purpose: Adrenal gland is a common site of metastasis and on the other hand, metastases are the most frequent malignant adrenal tumors. The aim of this study was to estimate the risk of malignancy in suspicious adrenal mass in patients with a history of cancer. Methods: This is a single-center retrospective analysis of patients with adrenal tumors treated previously for different types of cancers. Between 2004 and 2021 a hundred and six such patients were identified. Mean age of patients was 62.6 years (30-78), and mean time from oncologic treatment was 55.8 months (0-274). The most common primary cancer was kidney (RCC): 29 (27.4%), colon/rectum (CRC): 20 (18.9%) and lung (NSCLC): 20 (18.9%). Results: Of 106 patients, 12 had hormonally active (HA) (11,3%) and 94 (88,7%) non active (HNA) tumors In group of patients with HA tumours 4 had hypercortisolaemia and 8 had elevation of urinary metanephrines. In the first group of HA patients pathology confirmed preoperative diagnosis of adrenocortical cancer and no metastasis was found. In all patients from the second group pheochromocytomas were confirmed. Primary (PM) and secondary (SM) malignancies were found in 50 patients (47.2%). In hormone inactive group only SM - 46/94 (48.9%) were diagnosed. The odds that adrenal lesion was a metastasis were higher if primary cancer was RCC (OR 4.29) and NSCLC (OR 12.3). Metastases were also more likely with high native tumor density, and bigger size in CT. The cut-off values for tumor size and native density calculated from receiver operating characteristic (ROC) curves were 37mm and 24, respectively. Conclusion: Risk of malignancy of adrenal mass in a patient with a history of cancer is high (47,2%), regardless of hormonal status. 47,2% risk of malignancy. In preoperative assessment type of primary cancer, adrenal tumour size and native density on CT should be taken into consideration as predictive factors of malignancy. Native density exceeding 24 HU was the strongest risk factor of adrenal malignancy (RR 3.23), followed by history of lung or renal cancer (RR 2.82) and maximum tumor diameter over 37 mm (RR 2.14).

Can Color Doppler Ultrasound Be Effectively Used as the Follow-Up Modality in Patients Undergoing Splenic Artery Aneurysm Embolization? A Correlational Study between Doppler Ultrasound, Magnetic Resonance Angiography and Digital Subtraction Angiography.

Splenic artery aneurysm (SAAs) rupture is associated with a high mortality rate. Regular surveillance with imaging before and after intervention is crucial to guide best evidence treatment. The following study aimed to determine the efficacy of color Doppler ultrasound imaging (DUS) compared to digital subtraction angiography (DSA) and magnetic resonance angiography (MRA) as a follow-up modality after selective coil embolization of true SAAs. We analyzed data from 20 patients, 15 females (48.1 ± 16.1 years) undergoing selective SAA coil embolization using detachable fibered embolization coils. Imaging using DUS, MRA, and DSA was performed 3 months after the initial embolization or the consequent re-embolization procedure. Primary clinical success, defined as Class I aneurysm occlusion, on 3-month follow-up was seen in 16 (80.0%) patients. DUS had a sensitivity of 94.4% and a specificity of 42.9% when compared to DSA and 92.3% and 30%, respectively, when compared to MRA in identifying Class I aneurysm occlusion. The positive predictive value (PPV) of DUS in identifying the need for re-embolization was 75.0%, while the NPV of DUS in these terms was 90.5%. DUS showed a high sensitivity in detecting aneurysm occlusion and clinical success, simultaneously exhibiting poor specificity. Still, with caution, this follow-up modality could be used for monitoring select low-risk patients after selective embolization of SAAs. DUS could provide a higher cost-to-benefit ratio, enabling more systematic post-procedural follow-up, as it is far more commonly used compared to MRA and non-invasive compared to DSA.

Volumetric Flow Assessment in Doppler Ultrasonography in Risk Stratification of Patients with Internal Carotid Stenosis and Occlusion.

(1) Background: Alterations of blood flow volume in extracranial arteries may be related to the risk of occurrence of neurological symptoms. The aim of this study was the estimation of cerebral blood flow (CBF) in Doppler ultrasonography, as well as comparison of the flow volume in asymptomatic patients over 65 years old with ≥50%, and symptomatic patients with ≥70% internal carotid artery (ICA) stenosis, in order to assess whether the changes in the CBF correlates with the presence of neurological symptoms. (2) Methods: 308 patients over 65 years old were included in the retrospective cohort observational study: 154 asymptomatic with ≥50% ICA stenosis, 123 healthy volunteers, and 31 symptomatic referred for surgical treatment. The study group was split according to ICA stenosis (50-69%, 70-99% and occlusion). In all patients an extensive Doppler ultrasound examination with measurements of flow volume in common, internal, external carotid (ECA) and vertebral arteries (VA) was performed. (3) Results: Among asymptomatic (A) and symptomatic (S) patients with carotid stenosis 3 subgroups were identified: 57/154-37% (A) and 8/31-25.5% (S)-with significantly increased flow volume (CBF higher than reference range: average CBF + std. dev in the group of healthy volunteers), 67/154-43.5% (A) and 12/31-39% (S)-with similar to reference group flow volume (CBF within range average ± std.dev), and 30/154-19.5% (A) and 11/31-35.5% (S)-with decreased flow volume in extracranial arteries (flow lower than average-std.dev. in healthy volunteers). In symptomatic patients the percentage of patients with significant compensatory increased flow tends to raise with the severity of the stenosis, while simultaneous decline of number of patients with mild compensation (unchanged total CBF) is observed. The percentage of patients without compensation remains unchanged. In the group referred for surgical treatment (symptomatic, ≥70% ICA stenosis) the percentage of patients with flow compensation is twice as low as in the asymptomatic ones with similar degree of the ICA stenosis (8/31-25.8% vs. 26/53-49%, p = 0.04). Compensatory elevated flow was observed most frequently in ECA. (4) Conclusions: The presence of significant volumetric flow compensation has protective influence on developing ischaemic symptoms, including TIA or stroke. The assessment of cerebral inflow in Doppler ultrasonography may provide novel and easily accessible tool of identifying patients prone to cerebral ischaemia. The multivessel character of compensation with enhanced role of ECA justifies the importance of including this artery in the estimation of CBF.

Intracranial Flow Volume Estimation in Patients with Internal Carotid Artery Occlusion.

(1) Background: Carotid artery occlusion (CAO) in population studies has a reported prevalence of about 6 per 100,000 people; however, the data may be underestimated. CAO carries a significant risk of stroke. Up to 15% of large artery infractions may be secondary to the CAO, and in 27−38% of patients, ischaemic stroke is a first presentation of the disease. The presence of sufficient and well-developed collateral circulation has a protective influence, being a good prognostic factor in patients with carotid artery disease, both chronic and acute. Understanding the mechanisms and role of collateral circulation may be very important in the risk stratification of such patients. (2) Materials and Methods: This study included 46 patients (mean age: 70.5 ± 6 years old; 15 female, mean age 68.5 ± 3.8 years old and 31 male, mean age 71.5 ± 6.7 years old) with unilateral or bilateral ICA occlusion. In all patients, a Doppler ultrasound (DUS) examination, measuring blood flow volume in the internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery (VA), was performed. The cerebral blood flow (CBF) was compared to the previously reported CBF values in the healthy population >65 years old. (3) Results: In comparison with CBF values in the healthy population, three subgroups with CBF changes were identified among patients with ICA occlusion: patients with significant volumetric flow compensation (CBF higher than average + standard deviation for healthy population of the same age), patients with flow similar to the healthy population (average ± standard deviation), and patients without compensation (CBF lower than the average-standard deviation for healthy population). The percentage of patients with significant volumetric flow compensation tend to rise with increasing age, while a simultaneous decline was observed in the group without compensation. The percentage of patients with flow similar to the healthy population remained relatively unchanged. ICA played the most important role in volumetric flow compensation in patients with CAO; however, the relative increase in flow in the ICA was smaller than that in the ECA and VA. Compensatory increased flow was observed in about 50% of all patent extracranial arteries and was more frequently observed in ipsilateral vessels than in contralateral ones, in both the ECA and the VA. In patients with CAO, there was no decrease in CBF, ICA, ECA, and VA flow volume with increasing age. (4) Conclusions: Volumetric flow compensation may play an important predictive role in patients with CAO.

Volumetric Flow Assessment in Extracranial Arteries in Patients with 70-99% Internal Carotid Artery Stenosis.

Background: Cerebral blood flow (CBF) can be related to the risk of occurrence of neurological symptoms. Well-developed collateral circulation is a good prognostic factor in patients with cerebrovascular disease. Understanding the mechanisms of collateral circulation may be important in the diagnosis, treatment, and monitoring in this group of patients. The aim of this study covered the assessment of CBF in patients with 70−99% Internal carotid artery (ICA) stenosis, focusing on the circulation pathways and flow volume in extracranial arteries. Materials and methods: 53 patients with 70−99% ICA stenosis (mean age 73.4 ± 7 years old; 17 female, mean age 73.9 ± 7.5 years old; 36 male, mean age 73.2 ± 6.8 years old) were included in the study. In all patients a Doppler ultrasound (DUS) examination, measuring blood flow volume in the internal carotid artery (ICA), external carotid artery (ECA), and vertebral artery (VA), was performed. The cerebral blood flow (CBF) was compared to the previously reported CBF values in the healthy population > 65 years old. Results: Among the study groups three subgroups with flow differences were identified: patients with elevated CBF (significant volumetric flow compensation­26/53, 49%), patients with CBF similar to (mild compensation­17/53, 32%), and patients with CBF lower than (no compensation­10/53, 19%) the healthy, equally aged population. The percentage of patients with significant volumetric flow compensation was the highest in age groups 65−69 years old (62.5%) and >80 years old (60%). In the oldest age group (>80 years old) no patients without flow compensation (0%) were observed. The level of compensation depends on the number of the arteries with compensatory increased flow. In patients with significant volumetric flow compensation, the compensatory increased flow was observed, on average, in 3.31 arteries, in the mild compensation group­in 2.18 arteries, and in the no compensation group only in 1 artery. ICA plays the most important role in the volumetric flow compensation­the increase in the flow volume, in comparison to the reference values, was between 116.7 mL/min and 251.9 mL/min (in the ECA 57.6 mL/min−110.4 mL/min; in the VA 73.9 mL/min−104.9 mL/min). The relative flow increase was highest in the VA: 215−246%, then in the ECA: 163−206%, and finally in the ICA: 148.6−192%. The increased flow was most commonly observed in the VA­57 arteries, in second place in the ECA­42 arteries, and ICA­31 arteries. In patients with unilateral ICA stenosis, the volumetric flow increase was stated more frequently in the ipsilateral ECAs then in the contralateral ones (23 vs. 14). In the VA the opposite tendency was observed (29 contralateral vs. 23 ipsilateral). The ability of volumetric flow compensation decreased significantly with increasing age. Conclusions: Understanding the mechanisms of collateral circulation and their assessment in Doppler ultrasonography may provide a novel and easily accessible tool of identifying and monitoring patients with cerebrovascular disease.

5-Ethynyl-1-ß-D-ribofuranosyl-1H-[1,2,3]triazole-4-carboxylic acid amide (ETCAR) and its analogues: synthesis and cytotoxic properties.

Efficient Pd(0)-catalysed synthesis of 5-alkynyl-1-ß-D-ribofuranosyl-1H-[1,2,3]triazole-4-carboxylic acid amide depends on the presence of different protecting groups of the ribose moiety. Peracetylated 5-iodo substrate (15) couples with terminal alkynes or trimethyl-[(tributylstannyl)ethynyl]silane in 50-71% and 72% yield (ETCAR), respectively, although its hydrodehalogenation to 19 is noticeable. On the other hand, hydrodehalogenation of acetonide (16) predominates over coupling with terminal alkyne and slightly decreases a yield of cross-coupling reaction with trimethyl[(tributylstannyl)ethynyl]silane. Alternative conditions of reaction with terminal alkynes, to exclude so far identified hydride sources to produce hydridopalladium species, have been established for acetonide 16 and allowed to achieve 72% of coupling. Fluoromethyl derivative (42) was prepared from its 5-hydroxymethyl precursor by fluorination with DAST. Additionally, X-ray structural analysis of 42 was performed. All 1,2,3-triazolonucleosides and two synthesized cycloSal-pronucleotides were evaluated for cytotoxic activity against K562, HeLa and HUVEC cells.

Multiple occlusions in extracranial arteries in patients with aortic arch syndrome: is minimally invasive treatment still possible? Technical aspects of the treatment based on our own experience and a review of the literature.

Takayasu arteritis is a large vessel vasculitis of granulomatous nature and unknown aetiology affecting predominantly the aorta and its major branches, which may lead to ischaemic symptoms of many organs including the central nervous system. To decrease the risk of neurological complications and improve the quality of life, an arterial revascularisation may be necessary. The treatment options include pharmacotherapy as well as both open surgical and endovascular procedures, which has to be carefully chosen to obtain clinical success. There is an ongoing debate on the advantages, possibilities, and indications for implementing endovascular and open surgical methods, especially in high-risk patients. In this article we present our own experience in the treatment of an unusually complex and high-risk patient with multiple occlusion of supra-aortic branches, focusing on the technical aspects of the procedures and the decision-making process, as well as to confront with contemporary medical knowledge.