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Background and objective: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS–International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. Methods: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014–2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. Results: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44–47), 46.0% (42–50), 38% (35–41) and 37% (35–41), respectively; death was 19.2% (19–21), 15.3% (12.7–18.4), 29.2% (27–32) and 28.6% (27–31); and SICH was 3.6% (3–4), 4.4% (3.0–6.4), 5.8% (4.7–7.1) and not available. Conclusion: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies. © 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine

Background and purpose: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry. Methods: We compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0–1 at 3 months, (iii) functional independence defined as an mRS score of 0–2 at 3 months and (iv) 3-month mortality. Results: Out of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P > 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60–140) vs. 65 (IQR, 47–95) min, P < 0.001] and door-to-imaging [40 (IQR, 20–90) vs. 24 (IQR, 15–35) min, P < 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273). Conclusions: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS. © 2017 EAN

As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset (“golden hour”), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(−)] the “golden hour” by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24 h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24 h, respectively. A relative reduction in NIHSS-score of ≥40% at 2 h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0–1 at 3 months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(−) patients, with no differences in baseline characteristics (p > 0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p 0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53–11.03) and CREC (OR: 2.38; 95% CI 1.38–4.09), 24-h CR (OR: 1.88; 95% CI 1.08–3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15–3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement. © 2017, Springer-Verlag Berlin Heidelberg.

QUALITY OF STROKE CARE IN SLOVAKIA. Background: Intravenous thrombolysis (IVT) and endovascular treatment (EVT) significantly improve the outcome for ischaemic stroke (IS), but the results also depends on time. Quality control is therefore very important. Methods:We analysed the data from National stroke registry ( which is mandatory for all stroke centers in Slovakia) in March 2017 to evaluate the quality parameters. In the same time data from Registry of Stroke Care Quality in ESO EAST countries were analysed. Results:In 36 stroke centers 1108 patients were hospitalized, 987 with brain ischaemia (844 stroke, 143 u2013 TIA) and 117 with brain haemorrhage. The rate of acute treatment in IS (IVT, EVT, IVT+EVT) was 16,9% (IVT u2013 14,8 %, EVT u2013 3,3%). Door-to-needle time (DNT) uf0a3 20 minutes was in 31,1% of patients, 21-45 min. in 22,2%, 46-60 min. in 14,4% and u02c3 60 min. in 32,3% of patients. According SITS registry DNT in 2017 in Slovakia was 37 minutes, what is shorter than in 2016 (47 min.) and 2015 (50 min.). Of 730 patients with IS without AF 641 (88%) were discharged with antiplatelet agents, and of 217 patients with IS and AF 66,7% were discharged with anticoagulant treatment (Warfarin, NOAK), 8,5 % without antithrombotics, and 25,8% on LMWH. Conclusion:Our goal is to meet even better ESO quality criteria, therefore the Slovak stroke society in collaboration with Ministry of Health at the end of 2017 prepared new guidelines, set up a network of primary and secondary stroke centers and improved collaboration with rescue services.

BACKGROUND AND PURPOSE: According to the European license, alteplase can be given no sooner than 3 months after previous stroke. However, it is not known whether past history of stroke influences the effect of treatment. Our aim was to evaluate safety and functional outcome after intravenous thrombolysis administered in everyday practice to patients with previous stroke≤3 months compared with those with first-ever stroke. METHODS: We analyzed consecutive cases treated with alteplase between October 2003 and July 2014 contributed to the Safe Implementation of Thrombolysis for Stroke-Eastern Europe registry from 12 countries. Odds ratios were calculated using unadjusted and adjusted logistic regression. RESULTS: Of 13, 007 patients, 11, 221 (86%) had no history of stroke and 249 (2%) experienced previous stroke≤3 months before admission. Patients with previous stroke≤3 months had a higher proportion of hypertension and hyperlipidemia. There were no significant differences in outcome, including symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study (unadjusted odds ratio 1.27, 95% confidence interval: 0.74- 2.15), and being alive and independent at 3 months (odds ratio 0.81, 95% confidence interval: 0.61-1.09). CONCLUSIONS: Patients currently treated with alteplase, despite a history of previous stroke≤3 months, do not seem to achieve worse outcome than those with first- ever stroke. Although careful patient selection was probably of major importance, our findings provide reassurance that this group of patients may safely benefit from thrombolysis and should not be arbitrarily excluded as a whole. Further studies are needed to identify the shortest safe time lapse from the previous event to treatment with alteplase.

Background and Purpose - A recent meta-analysis investigating the association between statins and early outcomes in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) indicated that prestroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage. We investigated the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT. Methods - We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) registry on consecutive AIS patients treated with IVT during an 8-year period. Early clinical recovery within 24 hours was defined as reduction in baseline National Institutes of Health Stroke Scale score of ≥10 points. Favorable functional outcome at 3 months was defined as modified Rankin Scale scores of 0 to 1. Symptomatic intracranial hemorrhage was diagnosed using National Institute of Neurological Disorders and Stroke, European-Australasian Acute Stroke Study-II and SITS definitions. Results - A total of 1660 AIS patients treated with IVT fulfilled our inclusion criteria. Patients with statin pretreatment (23%) had higher baseline stroke severity compared with cases who had not received any statin at symptom onset. After adjusting for potential confounders, statin pretreatment was not associated with a higher likelihood of symptomatic intracranial hemorrhage defined by any of the 3 definitions. Statin pretreatment was not related to 3-month all-cause mortality (odds ratio, 0.92; 95% confidence interval, 0.57-1.49; P=0.741) or 3-month favorable functional outcome (odds ratio, 0.81; 95% confidence interval, 0.52-1.27; P=0.364). Statin pretreatment was independently associated with a higher odds of early clinical recovery (odds ratio, 1.91; 95% confidence interval, 1.25-2.92; P=0.003). Conclusions - Statin pretreatment seems not to be associated with adverse outcomes in AIS patients treated with IVT. The effect of statin pretreatment on early functional outcomes in thrombolysed AIS patients deserves further investigation. © 2015 American Heart Association, Inc.

BACKGROUND AND PURPOSE: Little is known about the effect of thrombolysis in patients with preexisting disability. Our aim was to evaluate the impact of different levels of prestroke disability on patients' profile and outcome after intravenous thrombolysis. METHODS: We analyzed the data of all stroke patients admitted between October 2003 and December 2011 that were contributed to the Safe Implementation of Treatments in Stroke-Eastern Europe (SITS-EAST) registry. Patients with no prestroke disability at all (modified Rankin Scale [mRS] score, 0) were used as a reference in multivariable logistic regression. RESULTS: Of 7250 patients, 5995 (82%) had prestroke mRS 0, 791 (11%) had prestroke mRS 1, 293 (4%) had prestroke mRS 2, and 171 (2%) had prestroke mRS≥3. Compared with patients with mRS 0, all other groups were older, had more comorbidities, and more severe neurological deficit on admission. There was no clear association between preexisting disability and the risk of symptomatic intracranial hemorrhage. Prestroke mRS 1, 2, and ≥3 were associated with increased risk of death at 3 months (odds ratio, 1.3, 2.0, and 2.6, respectively) and lower chance of achieving favorable outcome (achieving mRS 0-2 or returning to the prestroke mRS ; 0.80, 0.41, 0.59, respectively). Patients with mRS≥3 and 2 had similar vascular profile and favorable outcome (34% versus 29%), despite higher mortality (48% versus 39%). CONCLUSIONS: Prestroke disability does not seem to independently increase the risk of symptomatic intracranial hemorrhage after thrombolysis. Despite higher mortality, 1 in 3 previously disabled patients may return to his/her prestroke mRS. Therefore, they should not be routinely excluded from thrombolytic therapy.

Background and Purpose— DP-b99, a lipophilic moderate-affinity chelator of zinc, was postulated to improve recovery after acute ischemic stroke. We evaluated the safety and therapeutic effects of DP-b99 in patients with acute hemispheric ischemic stroke. Methods— The Membrane-Activated Chelator Stroke Intervention trial was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial of intravenous DP-b99 administered for 4 consecutive days (NCT00893867). Acute ischemic stroke patients within 9 hours of onset, but untreated by alteplase, with a baseline National Institutes of Health Stroke Scale score of 10 to 16, and evidence of language dysfunction, visual field defect, and neglect were eligible. The primary efficacy analysis compared distributions of functional status measured by modified Rankin score in the intent-to-treat population of patients with any post-treatment outcome, adjusted for initial severity. Functional and neurological recovery were secondary measures. Home time was an exploratory end point. Results— Enrollment terminated at n=446 after the planned interim analysis determined futility; follow-up continued. Final modified Rankin score distributions were equal between DP-b99 and placebo-treated groups ( P =0.10; P adj adjusted for baseline age and National Institutes of Health Stroke Scale=0.21). Fewer patients recovered to modified Rankin score ≤1 in the DP-b99–treated group (45/218; 20.6%) than after placebo (63/219; 28.8%) ( P =0.05; P adj =0.10). Similarly, fewer patients attained National Institutes of Health Stroke Scale ≤1 after DP-b99 (42/218; 19.3%) than placebo (56/219; 25.6%; P =0.10; P adj =0.26). Mortality was similar between DP-b99 and placebo intent-to-treat groups (36/218; 16.5% vs 33/219; 15.1%; P =0.68). Home time was unchanged by treatment (median 36 vs 36.5 days; P =0.25). Conclusions— Despite encouraging preclinical and phase II trial data, DP-b99 shows no evidence of efficacy in treating human ischemic stroke.

Background and Purpose Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients. Methods G-CSF (135 mu g/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were 9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size 15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging). Results G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1. Conclusions G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00927836.

Background: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. Methods and Results: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged ≥55 years, having suffered an ischemic stroke (≤3 months) or a transient ischemic attack (≤8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2–4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. Conclusions: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P

Summary The present paper investigated the effect of restricted feeding (11.00 to 13.00 h) by a single daily meal upon the activity of various oxidoreductases of the rat gastrio mucosa (SDH, α-GPDH, LDH, NADHTR), which at ad libitum feeding under normal lighting conditions with a dark night were shown to have distinct oircadian activity variations related to the rat's nooturnalfood intake preference (Zaviacic and Brozman 1978a). 1st part of the animals reoeived food in 2- h -period by natural daylight (naturallightingconditions), the 2nd part at the same period of time but in the dark (lighting oonditions reversed to natural). Checking the consumption of food, we found the animals to become adapted to the new time of food intake beginning with the 6th experimental day. The circadian rhthm of enzymes was examined on days 69, 83, 97, and 104 of limited feeding under the defined lighting schedule, at 06.00 h , 12.00 h , 18.00 h , and 24.00 h in groups of 5 animals. Synchronization of the highest dehydrogenases activities (particularly of SDH) with the time of restricted feeding was seen to develop in the gastrio mucosa of the rat. The synchronization effect was more pronounoed in the animals which received their food in the dark (and here even more in ♂ than in ♀). The effect of light during food intake was found to be rather interfering with the development of synchronization of dehydrogenase activities with the time of food intake, and this influence was again more marked in ♂ than in ♀. The time of food intake was at the feeding schedule restricted to daytime intake the main synchronizer for the circadian rhythm of oxidoreduotases of the gastric mucosa of the rat, with the highest daily activities recorded around the feeding time and the lowest activities at nightt which is the direct opposite of the circadian rhythm of the same enzymes determinedin rats fed ad libitum under normallightingconditions with a dark night.

Summary In the female urethra, the activity and distribution of 15 enzymes was determined by using both conventional and special histochemical methods. The enzymatic equipment differed according to the type of epithelial lining whose variation is characteristic for the female urethra. In the stratified squamous epithelium of the urethra, alkaline phosphatase, β-glucuronidase, acetyl-β-D-glycosaminidase, thiamine pyrophosphatase, and glucose-6-phosphatase exhibited but minimal or no activity, yet the other 10 enzymes studied displayed activity particularly in basally situated cells. Nearer to the lumen of the urethra, the activity in the epithelium kept decreasing and was mostly absent in superficial and desquamated cells. In the pseudostratified columnar and in the transitional epithelium of the urethra, the majority of enzymes showed an evenly distributed activity at all epithelial levels. In the apical parts of the most superficially situated cells bounding the lumen of the urethra, a distinct narrow zone of higher activity was observed. It was seen not only on determining the majority of dehydrogenases but also on examining acid phosphatase and naphthyl esterase. The endocrine cells occurring in the uroepithelial lining of the female urethra displayed, yet always with the exception of squamous epithelium (Zaviacic et al. 1983), distinct activity of acid hydrolytic enzymes, and of the enzymes studied it was particularly acid phosphatase. The majority of the demonstrated enzymes, of the dehydrogenases priority, is to be given to succinate dehydrogenase, enabled to differentiate readily between the highly active striated muscle fibers located in the most peripheral parts of the excisions along the urethral circumference and the smooth musculature of the urethral wall with a lower or only minimal activity.

The ultrastructure of rat parietal cells of the gastric mucosa was investigated during the twenty-four hours of a day. Male rats were housed at ad libitum feeding under normal light conditions with dark night. The animals were sacrificed at 6.00 h, 12.00 h, 18.00 h and 24.00 h respectively, in groups of 5 animals after standard 24 hours of starvation. From this material the electronograms of 356 parietal cells (19% in 6.00 h, 26% in 12.00 h, 21% in 18.00 h and 34% in 24.00 h samples) were evaluated. Based on literary data, the parietal cells were specified as secreting parietal cells (S, 38% of the total), secreting parietal cells returning to resting state (SR, 18% of the total), resting parietal cells (R, 35% of the total) and resting parietal cells tending to early secreting state (RS, 9% of the total). Some types of parietal cells are statistically highly significantly (x2 = 130.9, p less than 0.001) unequally distributed during the circadian rhythm: S are less numerous at 6.00 h (2% of the total) and 12.00 h (4% of the total) than expected (7 and 10% respectively), and more numerous at 18.00 h (11% of the total) and 24.00 h (21% of the total) than expected (8 and 13% respectively). Conversely, R are more numerous in the morning (13 and 15% instead of 7 and 9% respectively) and less in evening samples (4 and 3% instead of 7 and 12% respectively). Distribution differences were proved statistically (x2-test) for all cell-cell and hour-hour combinations expect the combinations S-RS and 6.00 h to 12.00 h. The maximal differences in distribution were found to be between the amounts of S and R at 6.00 h and 24.00 h (x2 = 77.3, p less than 0.001) and at 12.00 h and 24.00 h (x2 = 69.3, p less than 0.001). Thus, a distinct circadian rhythm of parietal cells, especially as to their fine cell structures involved in acid production was demonstrated. The results render further evidence of the rhythmicity of gastric acid production in rats.

Summary The simultaneous application of immunofluorescent and enzyme cytochemical methods made it possible to analyze the components of the walls of the arterial branches and arterial capillaries, and particularly the spongy arterial terminals in the red pulp of human spleen. The endothelium was identified by alkaline phosphatase demonstration, the basement membranes (BM) by means of antisera to glomerular BM , the media by using the same antisera, and the adventitia by means by antisera to hyaline cartilage, which are presumed to react particularly with adventitial structures. In the spongy arterial terminals visualized by means of anti-hyaline-cartilage antisera, the endothelium and mostly also BM , could be detected, yet the enzyme cytochemical reaction to acid phosphatase and α -naphthyl acetate esterase and the immunofluorescent reaction to lysozyme yielded negative reactions. The findings suggest that neither macrophages nor other cells containing the given enzymes in detectable form are accumulated in these structures.

In histological preparations commonly fixed in formaldehyde and embedded in paraffin which on immunofluorescent examination yielded results negative results or but very poor immunofluorescence, prominently positive results were obtained by chymotrypsin treatment on using the method of fluorescent antibodies. Corresponding results were also obtained in cryostat sections fixed for some min up to several days in formaldehyde so that immunofluorescence was completely negative. The positive immunofluorescent results indicate total or partial restoration of antigenicity of tissue proteins previously altered by formaldehyde.

The ultrastructure and certain cytochemical parameters of endocrine cells of the rat gastric mucosa during 168 h of fasting were investigated. To some of the fasting animals peroral food or alcohol was administered before decapitation. The EC (enterochromaffin cells) the ECL (enterochromaffin-like cells), D1 cells, AL (A-like cells) and G cells were identified by means of electron microscopy. Only the EC, ECL, and G cells could be identified by means of light microscopy by an adequate histochemical technique. The ultrastructural picture of the ECL and of the EC cells did not change markedly during the fasting. In the D1 cells there occurred an agglomeration of secretory granules. Some of them disintegrated and disappeared. In the AL cells an agglomeration of granules during the fasting was also observed. Granules engulfed in lysosomes were often found. The participation of lysosomes in the degradation of granules during the fasting was more marked in the AL cells than in the G cells. The participation of lysosomes was questionable in the EC and D1 cells, and in the ECL cells no lysosomes were observed. In contradistinction to the G cells of the non-fasting animals, where more than one half of the gastrin granules were "empty", the G cells during the fasting were filled with agglomerated dense granules and contained lysosomes with fragments of engulfed secretory granules. Following the administration of food (Larsen's diet) 3 h before sacrificing the dissolution of the content of granules with well preserved membranes was observed (emiocytosis did not take place). The administration of food did not lead to changes in the ultrastructural appearance of the EC cells. The peroral administration of alcohol did not lead to any changes in the ultrastructural appearance of the AL and G cells.

Summary Hyaline cartilage from the knee or rib of newborns was divided in neutral salts into a soluble and insoluble part. The insoluble part was treated with collagenase and was separated into 2 peaks by gel chromatography on Sephadex G-200 . The 1st peak revealed a low concentration of proteins, no hydroxyproline, and very high levels or uronates. In the 2nd peak, very high values of hydroxyproline and very low values of uronate were found. Thus the 1st peak contained only proteoglycans and no collagen, while the entire collagen was found in the 2nd peak. The individual fractions were inoculated into rabbits to obtain antibodies. Compared to the fraction containing macromolecular proteoglycans, antisera proved remarkably suitable particularly for analysis of human spleen, yet also of other organs. These anti-cartilage antisera visualized primarily spongy structures of pericapiIlary sheaths and circumferential reticulum of the periarterial lymphatic sheaths, but to a lesser extent also other extracellular structures of the spleen and of other organs.

Summary Immunohistochemical studies of paraffin sections of formaldehyde-fixed material and formalde hyde-fixed cryostat sections treated with trypsin or other enzymes were undertaken. Formaldehyde treatment resulted mostly in partial or total loss of antigenicity, as visualized by fluorescent antibody technique in tissue sections. The digestion of sections with trypsin resulted usually in total or partial restitution of antigenicity, previously altered with formaldehyde. This effect is suggested to consist primarily in breakirg formaldehyde-induced intermolecular cross-links. Restitution of antigenicity altered by formaldehyde can also be achieved on using pepsin or other proteolytic enzymes, or by some other technique. When the effect of one enzyme proves insufficient, it can readily be complemented by the action of another enzyme applied subsequently. Mild trypsin treatment preserves well the morphological structure of most tissues.

Differences in the morphological picture of the systemic anaphylactic reaction (SAR), and of the shock reaction induced by antigen-antibody (ag-ab) complexes in rabbits, are described. In rabbits SAR is characterized by acute distension of the lungs, with oedematous swelling in the vicinity of bronchi and veins, intravascular stasis of basophils without degranulation or visible fixation of the inducing antigen, small clusters of blood platelets, leukostasis, minimal decomposition of neutrophil granulocytes and absence of circulating or fixed ag-ab complexes. The shock reaction induced by ag-ab complexes is characterized by acute distension of the lungs without bronchospasm, swelling of the vicinity of bronchi and veins, hyaline thrombi particularly in the pulmonary microcirculation, leukostasis, formation of antigen-antibody complexes and thrombocyte clusters in the microcirculation, and by phagocytosis of these complexes and thrombocytes by various cells.

Summary The effect of distension of the stomach by air ( in vitro ) upon the ultrastructural picture of gastric endocrine cells in rats starved for 72 hours was investigated. Distension of the stomach by air in vitro , lasting for 5,10, 15 and 20 minutes, resulted in massive dissolution of gastrin granules that had accumulated in the course of starvation. In AL, D1, EC and ECL cells distension of the stomach by air failed to induce dissolution of granular content or release of granules by any other mechanism. In AL and D1 cells accumulation of secretory granules caused by starvation was observed, the ultrastructure of EC and ECL cells remained unchanged both under the effect of starvation and distension. Dilatation of endoplasmic reticulum profiles as well as other changes on some cell organelles observ-ved on endocrine cells after distension of the stomach by air in vitro are due to the effect of autolysis.

Summary An immunomicroscopic method combining the use of fluorescent antibodies and enzyme immunecomplex technique is presented. The basic steps of this procedure are: o 1. Rabbit antiserum (IgG) to the antigen to be determined, 2. FITC-conjugated antirabbit globulin, 3. Peroxidase + antiperoxidase complex, 4. 3,3-diaminobenzidine + H 2 O 2 . The method renders it possible to study simultaneously in the same section antigens and antibodies that are to be localized, and that both by immunofluorescent and immunoenzymatic techniques, it provide, means for further elimination of some of the deficiencies of immunofluorescent technique, and in suitable cases it also makes electronoptic examination available.

Summary The paper deals with the histochemical and cytochemical distribution of thiamine pyrophosphatase (TPP-ase 3.6.1.) in the normal rat gastric mucosa using the method of Novikoff and Goldfischer (1961). In light microscopy, activity was demonstrated only in the Golgi apparatus of the foveolar mucous cells; in the other specialized gastric mucosal cells no activity was established. At electron microscopic level, the reaction product was localized in the membranes of the cisternae of the Golgi apparatus of foveolar mucous cells, undifferentiated neck cells, parietal cells, chief cells and in endocrine cells. The reaction product was not found in the endoplasmic reticulum of any of the above mentioned types of cells with the exception of parietal cells. The deposits of the reaction product in the cytoplasmic membrane, in the capillary endothelium and on the surface of the plasma membrane of foveolar mucous cells represents the sites of activity of alkaline phosphatase. The examination of the TPP-ase in the gastric mucosa enables us to estimate the activity of the Golgi apparatus of gastric mucosal cells in the norm and in different pathological conditions connected with its changes.

Summary Examination of selected oxidoreductases (succinate dehydrogenase, mitochondrial glycerol—3-phosphate dehydrogenase, lactate dehydrogenase, NADH tetrazolium reductase) in the rat gastric mucosa revealed diurnal fluctuation of enzyme activities with the most marked manifestation in succinate dehydrogenase. The maximum enzymatic activity found at 18.00 h and 24.00 h 1) points to the highest oxidoreductase capacity in the parietal cells just at the time when a rat usually expresses spontaneously the highest interest in food intake. The high activity of succinate dehydrogenase and other enzymes at that time is very likely the expression of a “fixed” metabolic adaptation of the parietal cells to the elevated production of hydrochloric acid, in connection with its role in the digestion of food in the stomach. The low enzymatic activity of most rat parietal cells during the day may represent the picture of “a resting afunctional”.