Use of nitinol self-expandable stents in 26 dogs with tracheal collapse.

A study was designed to describe a novel approach to the treatment of tracheal collapse (TC) in dogs using self-expandable nitinol stents. Medical records were reviewed retrospectively for 26 client owned dogs in which nitinol stents were deployed. The entire length of trachea was supported independently of the extent of TC. Two overlapping stents were used instead of one in cases where one stent was not spanning the entire trachea adequately. The diameter of the cranial radiolucent portion of trachea, just behind the cricoid cartilage, was measured as a specific landmark to select the appropriate size of the stent. Two self-expandable nitinol stents were inserted in 9 of 26 dogs; the trachea in the rest of the cases was supported with only one stent. A follow up tracheoscopy was performed in 10 of 26 cases with recurrent clinical signs. Secondary tracheal stenosis in these cases was caused by stent fracture, granuloma or excessive stent shortening. Additional stents were placed successfully to expand the stenotic lumen. A support of the entire trachea may decrease risk of nitinol fracture at the end of the implant. Long term clinical improvement (25 of 26 dogs, 96 %) is comparable with the results of other studies.

Des stents auto-expansifs en nitinol ont été utilisés pour traiter 26 chiens atteints de collapsus trachéal et les résultats ont été évalués rétrospectivement. La trachée a été renforcée sur toute sa longueur, indépendamment de la localisation du collapsus. Si aucun stent d'une longueur suffisante n'était disponible, on a utilisé deux stents se recouvrant pour dilater l'ensemble de la trachée. Le diamètre du stent a été choisi sur la base du diamètre de la trachée directement caudalement au cricoïde. Chez 9 des 26 patients, on a posé deux stents se recouvrant. Chez tous les autres patients, il a été possible de renforcer la trachée sur toute sa longueur au moyen d'un seul stent. On a procédé chez dix patients à une seconde trachéoscopie, car de nouveaux signes de collapsus trachéal étaient apparus. Une sténose trachéale secondaire a été constatée suite à une fracture du stent, à du tissus de granulation ou à un raccourcissement excessif du stent. Un stent supplémentaire a été placé avec succès, pour dilater la lumière trachéale rétrécie. Le renforcement de la trachée sur toute sa longueur peut diminuer le risque de fracture du stent à son extrémité. L'amélioration clinique à long terme obtenue chez 25 des 26 patients (96 %) est comparable aux résultats d'autres études.

Distraction-stabilisation of two adjacent intervertebral spaces in a Dalmatian dog with caudal cervical spondylomyelopathy.

A 4-year-old, 40-kg, male, entire Dalmatian was presented for evaluation of chronic neck pain and pelvic limb ataxia. Myelography revealed ventrodorsal (hourglass) extradural compression over the intervertebral space between the 5th and 6th cervical vertebra and ventral extradural compression between the 6th and 7th cervical vertebra. Cranial compression disappeared and caudal compression markedly diminished after performing cervical traction. MRI scan confirmed protrusion of intervertebral discs and spinal cord compression in previously mentioned intervertebral spaces. Surgical distraction-stabilization of both intervertebral spaces was performed using threaded pins and polymethylmethacrylate. The convalescence from surgery was uneventful and the dog was walking without any signs of paresis until 5 months after surgery when radiography revealed implants loosening. The dog recovered fully of the implant removal and remained asymptomatic for more than 30 months.

Split staphylectomy to address soft palate thickness in brachycephalic dogs: 75 cases (2016-2018).

OBJECTIVES: Describe the split staphylectomy procedure to address soft palate thickness and assess the complications and long-term outcome of this procedure as a part of multi-level surgery for brachycephalic obstructive airway syndrome. To consider whether same-day discharge following this surgery can be recommended. MATERIALS AND METHODS: Medical records of dogs treated for brachycephalic obstructive airway syndrome using the split staphylectomy were reviewed. Owners were contacted to complete a questionnaire assessing initial postoperative concerns, the long-term outcome and the effect of surgery on their dog's quality of life. RESULTS: Seventy-five dogs underwent split staphylectomy during the study period. The overall complication rate was 8.3%, of which 2.7% were considered major. No life-threatening complications occurred, and no complications were related to the staphylectomy. The questionnaire was completed by 66.7% of owners (median follow-up 459 days), of which 88% felt that surgery had improved the quality of life for their dog. The majority (88%) of dogs were discharged from hospital on the day of surgery. Of the surveyed owners, 14% sought veterinary attention between their dog leaving the hospital and the scheduled postoperative reassessment 2 weeks after surgery. Four dogs were presented for veterinary intervention during this time period, but no intervention was related to the staphylectomy or for a life-threatening condition. CLINICAL SIGNIFICANCE: The split staphylectomy offers a safe, straightforward method of addressing both excess thickness and length of soft palate in dogs with brachycephalic obstructive airway syndrome. Dogs can be discharged on the same day as brachycephalic obstructive airway syndrome surgery including split staphylectomy without an increased risk of complications.

EFFECT OF RANIBIZUMAB AND AFLIBERCEPT ON RETINAL PIGMENT EPITHELIAL DETACHEMENT, SUBRETINAL AND INTRARETINAL FLUID IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The aim of the study was to compare the effect of three initial doses of the anti-VEGF ranibizumab and aflibercept medication on serous pigment epithelial detachment (PED), subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula of treatment naive neovascular AMD (nvAMD) patients. MATERIAL AND METHODS: The cohort consists of 148 patients, of which 74 patients were treated with ranibizumab (51 females and 23 males) and 74 with aflibercept (46 females and 28 males). The data was recorded prospectively from the moment of diagnosis and start of treatment for a period of 3 months. At the moment of diagnosis and 3 months later, an OCT examination (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was performed. The OCT examination included a macular scan with 25 scans. Using the OCT instrument software, we measured the maximum anterior-posterior elevation of serous PED, the highest thickness of SRF and the largest diameter of the intraretinal cystic space. The statistical significance of differences between groups was evaluated using the t-test for continuous data and the Fisher exact test for categorical data. Changes in values of continuous variables over time were evaluated using the Wilcoxon paired test. Paired comparisons of binary parameters were determined by the McNemar test. RESULTS: Full regression of PED, SRF and IRF occurred in 3 (4.1%), 25 (39%) and 20 (51%) patients treated with ranibizumab, and in 5 (7.9%, p = 0.470), 28 (47%, p = 0.470) and 25 (57%, p = 0.827) patients treated with aflibercept, respectively. The average regression of PED, SRF and IRF was -60.4 μm (median -37.5 μm), -84.3 μm (median -85 μm) and -109.3 μm (median -81 μm) in patients treated with ranibizumab, and -46.3 μm (median -30 μm, p = 0.389), -127.7 μm (median -104 μm, p = 0.096) and -204.4 μm (median -163 μm, p = 0.005) in patients treated with aflibercept, respectively. We did not show a statistically significant difference in the regression rates of PED, SRF and IRF between the ranibizumab and aflibercept groups. (in patients with IRF after adjustment of the higher baseline IRF volumes in patients treated with aflibercept, p = 0.891). CONCLUSION: We are convinced that ranibizumab and aflibercept have the same effect on serous PED, SRF and IRF in the macula in patients with treatment naive nvAMD during the initial loading phase.

Molecular-level insight into hot-melt loading and drug release from mesoporous silica carriers.

Drug amorphisation by loading to inorganic mesoporous carriers represents an emerging area of improving the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). In this work, for the first time, a molecular-level insight into the process of API loading to mesoporous SiO2 (silica) carriers by the hot-melt impregnation method and its subsequent release during dissolution was obtained using ATR-FTIR spectroscopic imaging. A physical mixture of ibuprofen crystals and mesoporous silica particles was heated and the dynamics of melt loading into the silica pore structure was directly observed in situ by ATR-FTIR spectroscopic imaging. The loss of crystallinity, the redistribution of the API in the silica pore network and the subsequent stabilisation of the amorphous form upon cooling were proven. The API was involved in two different kinds of molecular-level interactions: API dimers in the amorphous bulk, and individual API molecules adsorbed on the silica surface. The melt-loaded silica carriers were comprehensively characterised by DSC, SEM and dissolution tests, which proved dissolution rate enhancement due to amorphisation of the API. Drug release form the hot-melt loaded mesoporous silica carriers was observed in real time and the conditions leading to local re-crystallisation of super-saturated solution of the API were identified.

Combined cytotoxicity effect of hyperthermia and anthracycline antibiotics on human tumor cells.

The effects of temperature on the anthracycline antibiotics-induced cell kill of DND-1A human malignant melanoma (MM) and DND-39A Burkitt's lymphoma (BL) cell lines were studied by means of a clonogenic assay. The two cell lines differed in sensitivity when exposed to heat: The MM cells were unaffected by hyperthermia (42 degrees C), whereas BL cells were sensitive to this temperature. With the MM cells, hyperthermia potentiated the cytotoxic effects of doxorubicin (ADM), daunorubicin, mitoxantrone (DHAD), and quelamycin but did not enhance that of aclacinomycin (ACM). Conversely, the exposure of cells to the anthracycline compounds at 0 degree C resulted in almost complete disappearance of cell kill effects except with ACM; ACM retained substantial cell kill effects even at the given low temperature. For BL cells, ADM- or DHAD-induced cell lethality was also potentiated by hyperthermia; ACM produced only additive cell kill. At 0 degree C, ACM's effects virtually disappeared. These data indicate that human tumor cell lines have a substantial variety in heat sensitivity and that not every anthracycline antitumor agent is potentiated by temperature. ACM's thermoresponse is unique among anthracycline antibiotics studied. Additionally, it was shown that normothermic cell kill by ADM was not affected by hyperthermic preheating; however, preheating of appropriate duration produced important influence on subsequent hyperthermic ADM-induced cell kill.

Transplantation of human malignant mesothelioma into nude mice.

Human pleural malignant mesothelioma was successfully transplanted into nude mice from 2 of 3 patients. The tumor implants of the first generation grew in 6 of 20 mice (30%), with a take of implants of 17 of 32 (53%). Overall, tumors grew from 52 of 80 mice (65%) in a total of 169 of 266 implants (64%) during the first four generations. The mean delay between transplantation and tumor growth was 46 days (range, 18 to 104 days). Pathological examination by light and electron microscopy confirmed the nature of the growing tumors in nude mice. Pathology of transplanted tumors was grossly similar to the human tumors in both first- and second-generation transplants. Up to eight generations have been presently carried out with presence of a human karyotype in transplanted tumors. The potential usefulness of this model with particular reference to chemosensitivity of these tumors will be investigated.

The effect of structural modifications of 5-fluorouracil derivatives on their transport and biodegradation by isolated rat jejunum.

The continuous-perfusion technique was used in an isolated segment of everted rat jejunum to study transport and biotransformation processes in a series of cancerostatic derivatives of 5-fluorouracil. Metabolic alterations during penetration of the intestinal wall were assessed by high-performance liquid chromatography (HPLC). Octanol-buffer partition coefficients were measured, and the lipophilicity of the study compounds and fragmental constants for their sugar moieties were assessed. In the present series of 5-fluorouracil derivatives, there was no correlation between lipophilicity and metabolic cleavage to 5-fluorouracil, but a correlation was found between lipophilicity and the transport rate. Remarkable stability of the nucleoside bond and high biotransport were observed with 5'-chloro-5-fluorouridine, suggesting a different mode of activation for this derivative.

Structure-intestinal transport and structure-metabolism correlations of some potential cancerostatic pyrimidine nucleosides in isolated rat jejunum.

Both transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2'-deoxyribonucleosides, and acetyl and 5'-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5'-Halogeno and 5'-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r = 0.99, n = 5).

Comparative study of cyclocytidine and arabinosylcytosine disposition in rats.

The stability of cyclocytidine (II) in aqueous solutions decreased with increasing pH and temperature. After intravenous injection to rats the biphasic decline of cyclocytidine in the serum was accompanied by simultaneous formation of arabinosylcytosine. Since under physiological conditions (37 degrees C, pH 7.2) the half-lifetime of cyclocytidine dissolved in water was 5 hours, the very early appearance of arabinosylcytosine in the serum of rats suggests that various hydrolytic enzymes may also be responsible for the conversion of cyclocytidine in to arabinosylcytosine in vivo. An equimolar dose of arabinosylcytosine (I) injected to rats produced serum levels which were several times higher than those of cyclocytidine under the same conditions. Since the rate constant of overall elimination was similar for both compounds, this difference in serum levels may most probably be explained by a much higher distribution volume of cyclocytidine resulting also in a higher plasmatic clearance of this compound.

Ingrowth of hyperplastic capillary sprouts into fibrin clots: further evidence in favor of the angiogenic hypothesis of repair and fibrosis.

According to the conventional hypothesis and its variants, wound granulation tissue is formed by the proliferation and the migration of two closely cooperating but separated cell systems: the endothelial and the fibroblastic (including pericytes). While the elaborated theory of angiogenesis explains the former, there is not a similar theory concerning the latter. The recently proposed angiogenic hypothesis of repair and fibrosis unifies both cell systems by proposing endothelial origin for fibroblastic cells. It was formed on the basis of hyperplastic capillaries and vascular endothelium derived fibroblastic cells in chronic fibrotic diseases. The recent description of hyperplastic capillary sprouts in experimental fibrin clots confirms the validity of this hypothesis also in healing by primary and secondary intentions.

Unattainable homeostasis in healing leads to interstitial and vascular intimal fibroses: a unified hypothesis of their pathogenesis.

Homeostasis, or the maintenance of constant internal environment in the organism, is disrupted by injury. In this case, pathological defence reactions such as inflammation and healing take place in order to restore it. They succeed if etiological harmful factors are eliminated. In the opposite case, constant injury leads to continuous healing and fibrosis. Both interstitial and vascular intimal fibroses have similar pathogeneses and may be provoked by the same etiological factors. It may be concluded, therefore, that in spite of their apparent differences, both fibroses are only the different expressions of the same process by which injury should be healed and homeostasis restored. Fibrosis itself may become dangerous for the patient, depending on its extent and on the affected organ. In this case, the inhibition of healing reaction by antiangiogenesis may be envisaged as a life-saving measure.

A study on structure-activity relationships of nucleoside analogues.

A selected series of nucleoside analogues were tested for inhibitory activity vs DNA and/or RNA synthesis at L1210 cells. The structure-activity relationship was studied among derivatives of 5-fluorouracil and arabinosylcytosine (araC), compounds clinically used in cancer chemotherapy. 5-Fluorouridine was found to be a selective, most potent inhibitor of RNA synthesis. Arabinosylcytosine was the most potent selective inhibitor of DNA synthesis. Only cyclocytidine stands very close to the carcinostatic antibiotics in its strong simultaneous inhibition of both DNA and RNA synthesis. A biologically interesting new group of 5'-deoxy derivatives of arabinosylcytosine was investigated. The inhibitory activity vs DNA and/or RNA synthesis is compared with the activity against growth of E. coli and against herpes simplex virus type I (HSV). The system for inhibition of NA synthesis is proposed as a preliminary first step: an in vitro screening method promising for the discovery of new types of potential carcinostatic agents. Both transport and biotransformation processes of nucleoside analogues were studied in the isolated everted rat jejunum with a continuous perfusion technique. The 5'-substituted derivatives of araC and 5'-chloro-5-fluorouridine exhibited higher transport rates and higher metabolic stability during intestinal penetration than the parent nucleosides. There was found to be no correlation between lipophilicity and transport rate, but there is a correlation between lipophilicity and metabolic alterations among the nucleoside derivatives studied.

Antiviral activities of pyrimidine nucleoside analogues: some structure--activity relationships.

Seventeen nucleoside derivatives (derived from arabinosylcytosine, resp. cytidine, 5-fluorouracil and uracil) were tested by agar-diffusion plaque-inhibition test for their antiviral activity with herpes simplex, vaccinia, fowl plague, Newcastle disease and western equine encephalomyelitis viruses. The highest antiviral activity against DNA viruses exhibited arabinosylcytosine, N4-acylarabinosylcytosines, arabinosylthiouracil, cyclocytidine and its 5'-chloroderivative. RNA viruses were inhibited by 5-fluorouridine only, whereas other tested compounds were ineffective or showing marginal activity only. By search for relationship between chemical structure and antiviral activity a tendency was found of higher antiviral activity at lower lipophilicity. This is probably due to better transport of the studied compounds into cell. The chemical structure, however, is the main reason of antiviral activity.

[Evaluation of bacterial colonization of the conjunctival sac in ranibizumab intravitreal injections treated patients]. / Hodnocení bakteriálni kolonizace spojivkového vaku pacientu lécených intravitreálními injekcemi anibizumabu.

AIM: To establish the conjunctival sac bacterial flora structure in patients with wet form of the age-related macular degeneration (ARMD) indicated for the intravitreal application of Ranibizumab (Lucentis, Novartis Pharma AG). To evaluate the efficacy of combined local preparation with broad-spectrum antibiotic moxifloxacine 0.5% (Vigamox, Alcon) and povidone iodine solution, 5% (Betadine, Egis Pharmaceuticals, LTD.) and to evaluate subjective toleration of moxifloxacin. MATERIALS AND METHODS: In a prospective, non-randomized study were evaluated 20 eyes of 20 patients treated by means of intravitreally-applied ranibizumab. In all patients, the swabs from the conjunctival sac of the treated eye were repeatedly taken in a given time-schedule--before the start of using moxifloxacin, on the day of the intravitreal application of ranibizumab--before the irrigation of the conjunctival sac with povidone iodine solution, 5%, further after the irrigation--immediately before the injection and the control was token three days after the intravitreal injection. At the same time, the moxifloxacine toleration was evaluated by a questionnaire. RESULTS: The samples taken from the conjunctival sac of the treated eye before the application of moxifloxacine had positive bacterial culture in 17 eyes (85%) and negative culture in 3 eyes (15 %). Furthermore, in 2 eyes with positive culture, there was established resistance to moxifloxacine. After 3 days of moxifloxacine application, there was negative culture in 13 eyes (65%), in 7 eyes (35%) was the bacterial cultivation positive. After the irrigation with povidone iodine 5% solution was the cultivation negative in 17 eyes (85%), positive cultivation was in 3 eyes (15%); in all three cases, the cultures were susceptible to moxifloxacine. Three days after the intravitreal injection, the negative cultivation from the conjunctival sac was found in 13 eyes (65%), and in 7 eyes was the cultivation positive; the cultivated bacteria were moxifloxacine susceptible. Subjective symptoms after moxifloxacine application were reported by 10 patients altogether; 5 patients were without symptoms and 5 patients did not return the questionnaire. On average, the symptoms started the second day of moxifloxacine treatment and the average grade of symptoms was 1.6 on the scale from 0 to 5. CONCLUSION: In our group we found a broad spectrum of microorganisms colonizing the conjunctival sac of patients indicated to the ARMD intravitreal treatment. After the prophylaxis with moxifloxacine, the incidence of positive bacterial cultivation decreased and the povidone iodine 5% solution irrigation this effect increased. The most common pathogen species was Staphylococcus coagulasis negative. Although the resistance to moxifloxacine in two different bacteria in two eyes in the beginning of observation was established, after moxifloxacine treatment, the cultivation of these bacteria in both eyes was negative, and in all other cases the cultivated bacteria were susceptible to moxifloxacine.

Determination of polycyclic aromatic hydrocarbons and their oxy-, nitro-, and hydroxy-oxidation products.

A sensitive method has been developed for the trace analysis of PAHs and their oxidation products (i.e., nitro-, oxy-, and hydroxy-PAHs) in air particulate matter (PM). Following PM extraction, PAHs, nitro-, oxy-, and hydroxy-PAHs were fractionated using solid phase extraction (SPE) based on their polarities. Gas chromatography-mass spectrometry (GC-MS) conditions were optimized, addressing injection (i.e., splitless time), negative-ion chemical ionization (NICI) parameters, i.e., source temperature and methane flow rate, and MS scanning conditions. Each class of PAH oxidation products was then analyzed using the sample preparation and appropriate ionization conditions (e.g., nitro-PAHs exhibited the greatest sensitivity when analyzed with NICI-MS while hydroxy-PAHs required chemical derivatization prior to GC-MS analysis). The analyses were performed in selected-ion-total-ion (SITI) mode, combining the increased sensitivity of selected-ion monitoring (SIM) with the identification advantages of total-ion current (TIC). The instrumental LODs determined were 6-34 pg for PAHs, 5-36 pg for oxy-PAHs, and 1-21 pg for derivatized hydroxy-PAHs using electron ionization (GC-EI-MS). NICI-MS was found to be a useful tool for confirming the tentative identification of oxy-PAHs. For nitro-PAHs, LODs were 1-10 pg using negative-ion chemical ionization (GC-NICI-MS). The developed method was successfully applied to two types of real-world PM samples, diesel exhaust standard reference material (SRM 2975) and wood smoke PM.