Patterns and Incidence of Pneumonitis and Initial Treatment Outcomes with Durvalumab Consolidation Therapy after Radical Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer.

Durvalumab consolidation after chemoradiotherapy for stage III non-small cell lung cancer (NSCLC) has become the standard of care. Single-center results were examined for treatment outcomes and patterns of pneumonitis in clinical practice. Patients with stage III NSCLC who underwent chemoradiotherapy at our institution (n = 150) were included. The patients were treated with chemoradiotherapy and durvalumab consolidation (Group D, n = 69) or chemoradiotherapy alone (Group N, n = 81). The overall survival (OS), progression-free survival (PFS), and the incidence of and risk factors for 12-month pneumonitis grade ≥ 2 (G2) were investigated. Two-year OS rates were 71.6% in Group D and 52.7% in Group N (p = 0.052). Two-year PFS rates were 43.0% in Group D and 26.5% in Group N (p = 0.010), although a propensity score matched analysis showed no significant difference. The incidence of 12-month pneumonitis ≥ G2 tended to be higher in Group D than in Group N (41.9% vs. 26.3%, p = 0.080). However, there was no difference in pneumonitis ≥ G3 rates (10.5% vs. 12.6%, p = 0.657). A multivariate analysis showed that the lung volume spared from 5 Gy (VS5) < 1800 cm3 was a risk factor for pneumonitis ≥ G2 in Group D. Durvalumab consolidation showed the potential to prolong PFS without increasing the severity of pneumonitis.

Analysis of adverse events related to extracorporeal membrane oxygenation from a nationwide database of patient-safety accidents in Japan.

Although adverse events related to extracorporeal membrane oxygenation have been reported, epidemiological data on life-threatening events are insufficient to study the causes of such adverse events. Data from the Japan Council for Quality Health Care database were retrospectively analyzed. The adverse events extracted from this national database included events associated with extracorporeal membrane oxygenation reported between January 2010 and December 2021. We identified 178 adverse events related to extracorporeal membrane oxygenation. At least 41 (23%) and 47 (26%) accidents resulted in death and residual disability, respectively. The most common adverse events were cannula malposition (28%), decannulation (19%), and bleeding (15%). Among patients with cannula malposition, 38% did not undergo fluoroscopy-guided or ultrasound-guided cannulation, 54% required surgical treatment, and 18% required trans-arterial embolization. In this epidemiological study in Japan, 23% of the adverse events related to extracorporeal membrane oxygenation had fatal outcomes. Our findings suggest that a training system for cannulation techniques may be needed, and hospitals offering extracorporeal membrane oxygenation should perform emergency surgeries.

Development of a Manufacturing Process toward the Convergent Synthesis of the COVID-19 Antiviral Ensitrelvir.

We describe the development of the practical manufacturing of Ensitrelvir, which was discovered as a SARS-CoV-2 antiviral candidate. Scalable synthetic methods of indazole, 1,2,4-triazole and 1,3,5-triazinone structures were established, and convergent couplings of these fragments enabled the development of a concise and efficient scale-up process to Ensitrelvir. In this process, introducing a meta-cresolyl moiety successfully enhanced the stability of intermediates. Compared to the initial route at the early research and development stage, the overall yield of the longest linear sequence (6 steps) was improved by approximately 7-fold. Furthermore, 9 out of the 12 isolated intermediates were crystallized directly from each reaction mixture without any extractive workup (direct isolation). This led to an efficient and environmentally friendly manufacturing process that minimizes waste of organic solvents, reagents, and processing time. This practical process for manufacturing Ensitrelvir should contribute to protection against COVID-19.

Countering hemorrhagic shock due to duodenal variceal rupture with resuscitative endovascular balloon occlusion of the aorta.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) has become an important option for managing life-threatening, traumatic or non-traumatic, arterial bleeding. The use of REBOA in variceal hemorrhagic shock, however, has rarely been reported. A 54-year-old man with untreated alcoholic liver cirrhosis presented with hematochezia and altered mental status. Contrast-enhanced computed tomography suggested ruptured duodenal varices. Since the patient had profound hypotension, we performed REBOA to temporize the hemorrhage. Immediately after balloon inflation, his blood pressure increased, allowing us to safely perform endoscopic variceal ligation. Our case indicates that REBOA is effective in controlling portal venous flow in acute gastrointestinal variceal hemorrhage.

Sensorineural hearing dysfunction after discharge from critical care in adults: A retrospective observational study.

BACKGROUND: Patients undergoing intensive care are exposed to risk factors for hearing impairment. This study assessed the worse changes in pure tone average (PTA) thresholds after intensive care and identified the factors associated with worse hearing function. METHODS: We conducted a single-centre retrospective study, and included adult patients admitted to the intensive care unit (ICU) of Kurashiki Central Hospital between January 2014 and September 2019, who had regular pure tone audiometry performed before and after ICU admission. Correlations between changes in PTA threshold and patient characteristics, were evaluated. The included ears were classified as those with worse hearing (>10 dB increase in the PTA threshold) and those without worse hearing, and the baseline characteristics were compared. RESULTS: During the study period, 125 ears of 71 patients (male:female ratio, 35:36; mean age, 72.5 ± 12.3 years) met the eligibility criteria. Age, sex, and the use of furosemide were not correlated with changes in PTA threshold. Univariate analysis showed that ears with worse hearing were associated with a lower serum platelet count than ears without worse hearing (153 ± 85 × 109/L vs. 206 ± 85 × 109/L, respectively; P = 0.010), and the rate of planned ICU admission (elective surgery) was higher in the worse hearing group (57.1% vs. 28.8%, respectively; p = 0.011). CONCLUSIONS: Age, sex, and the use of furosemide did not have adversely affect hearing function. Low serum platelet count and planned admission appear to be risk factors for worse hearing.

The association between ERK inhibitor sensitivity and molecular characteristics in colorectal cancer.

The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical response is not always associated with the molecular signature. The patient-derived organoids (PDO) have emerged as a powerful in vitro model system to study cancer, and it has been widely applied for the drug screening. The present study aims to analyze the association between the molecular characteristics which analyzed by next-generation sequencing (NGS) and sensitivity to the ERK inhibitor (i.e., SCH772984) in PDO derived from CRC specimens. A drug sensitivity test for the SCH772984 was conducted using 14 CRC cell lines, and the results demonstrated that the sensitivity was in agreement with the BRAF mutation, but was not completely consistent with the KRAS status. In the drug sensitivity test for PDO, 6 out of 7 cases with either BRAF or KRAS mutations showed sensitivity to the SCH772984, while 5 out of 6 cases of both BRAF and KRAS wild-types were resistant. The results of this study suggested that the molecular status of the clinical specimens are likely to represent the sensitivity in the PDOs but is not necessarily absolutely overlapping. PDO might be able to complement the limitations of the gene panel and have the potential to provide a novel precision medicine.

Inhibition of Plasmodium falciparum Lysyl-tRNA Synthetase via a Piperidine-Ring Scaffold Inspired Cladosporin Analogues.

Plasmodium falciparum lysyl-tRNA synthetase (PfKRS) represents a promising therapeutic anti-malarial target. Cladosporin was identified as a selective and potent PfKRS inhibitor but lacks metabolic stability. Here, we report chemical synthesis, biological evaluation and structural characterization of analogues where the tetrahydropyran (THP) frame of cladosporin is replaced with the piperidine ring bearing functional group variations. Thermal binding, enzymatic, kinetic and parasitic assays complemented with X-ray crystallography reveal compounds that are moderate in potency. Co-crystals of Cla-B and Cla-C with PfKRS reveal key atomic configurations that allow drug binding to and inhibition of the enzyme. Collectively these piperidine ring scaffold inhibitors lay a framework for further structural editing and functional modifications of the cladosporin scaffold to obtain a potent lead.

Effect of Half-Heusler Interfacial Structure on Thermal Transport Properties of (Ti, Zr)NiSn Alloys.

The microstructure of the half-Heusler phase separation in half-Heusler (HH) MNiSn(M = Ti, Zr) intermetallic compounds has been investigated systematically in this study. Scanning electron microscopy observations from a range of (Tix, Zr1-x)NiSn have revealed the HH single phase at high temperature formed into many HH domains of various HH compositions with different Ti/Zr concentration ratios when x > 0.1. The formation of Ti-rich and Zr-rich HH domains with rather large size (up to several hundred µm in diameter) is thought to originate from a combination of the liquid solidification process and followed by an HH phase decomposition process within a miscibility gap between the TiNiSn and ZrNiSn HH phases. We have noticed that in addition to the mass and size difference based phonon scattering, sharp interfaces between the Ti-rich and Zr-rich HH domains containing high density of misfit dislocations could provide additional phonon scattering centers and reduced thermal conductivity of the alloys. Moreover, the cyclic heat treatment process at temperatures near the HH phase-decomposition's critical temperature could modify the HH domains' microstructure to become more diffuse, coherent with a more comprehensive length scale, and globular shape. These diffuse and coherent Ti-rich HH1/Zr-rich HH2 interfaces can provide an additional enhancement of phonon scattering and thereby result in a more considerable reduction of thermal conductivity than those of relatively less diffuse ones. We anticipate a similar approach of using cyclic heat treatment to modify the microstructure and consequently lead to further enhancement of phonon scattering can also apply to many other thermoelectric alloy systems possessing a miscibility gap.

Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors.

BACKGROUND: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). METHODS: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). RESULTS: The median follow-up time was 24 (range: 1-124) months. The median prescribed dose was 60 (6-70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0-87.6; SCRT: 50.4, 95% CI: 27.6-73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7-85.2; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2-86.4; SCRT: 42.0, 95% CI: 17.7-70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups. CONCLUSIONS: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Etiology and mortality in severe acute pancreatitis: A multicenter study in Japan.

BACKGROUND/OBJECTIVES: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. METHODS: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. RESULTS: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. CONCLUSIONS: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Conformational heterogeneity in apo and drug-bound structures of Toxoplasma gondii prolyl-tRNA synthetase.

Prolyl-tRNA synthetase (PRS) is a member of the aminoacyl-tRNA synthetase family that drives protein translation in cells. The apicomplexan PRSs are validated targets of febrifugine (FF) and its halogenated derivative halofuginone (HF). PRSs are of great interest for drug development against Plasmodium falciparum and Toxoplasma gondii. In this study, structures of apo and FF-bound T. gondii (TgPRS) are revealed and the dynamic nature of the conformational changes that occur upon FF binding is unraveled. In addition, this study highlights significant conformational plasticity within two different crystal structures of apo PRSs but not within drug-bound PRSs. The apo PRSs exist in multi-conformational states and manifest pseudo-dimeric structures. In contrast, when FF is bound the PRS dimer adopts a highly symmetrical architecture. It is shown that TgPRS does not display extant fold switching, in contrast to P. falciparum PRS, despite having over 65% sequence identity. Finally, structure-comparison analyses suggest the utility of r.m.s.d. per residue (r.m.s.d./res) as a robust tool to detect structural alterations even when the r.m.s.d. is low. Apo TgPRS reveals FF/HF-induced rigidity and this work has implications for drug-design studies that rely on the apo structures of target proteins.

Unilateral loss of thoracic motion after blunt trauma: a sign of acute Brown-Séquard syndrome.

Late-onset Brown-Séquard syndrome (BSS) is a rare condition resulting from a spinal cord injury that develops weeks to years after a blunt trauma. Acute-onset BSS after a blunt injury has been rarely reported. Here, we report on a case of BSS, in a 58-year-old man, that developed immediately after a motor vehicle accident. Upon admission, loss of right thoracic motion, complete right paresis, and loss of pain and temperature sensations below the C3 level on the left side were observed. Magnetic resonance imaging showed hyperintensities within the cervical spinal cord at the C2-C3 level, confirming the diagnosis of BSS. Thoracic motion rapidly recovered, but other neurological sequelae persisted. BSS related to cervical cord injury should be suspected when patients develop hemiparesis and contralateral sensory loss immediately after a blunt trauma. Likewise, clinicians should be aware that unilateral loss of thoracic motion could be an important sign of BSS.

Radiation Therapy for Uterine Cervical Cancer With Lung Metastases Including Oligometastases.

BACKGROUND/AIM: To investigate the role and outcomes of radiation therapy (RT) for stage IVB uterine cervical cancer (UCC) patients with lung (oligo) metastases due to the lack of recent reports on the subject. PATIENTS AND METHODS: The cohort for this retrospective study comprised 23 consecutive patients with UCC (squamous cell carcinoma, n=13) and lung metastases who had received pelvic RT. Ten had lung metastases only, including 7 with oligometastases (≤4 lung metastases); the remaining 13 also had other distant metastases. RESULTS: Nine (39.1%) of the 22 patients (95.7%) completed RT without interruption. The 1-year primary progression-free rate was 95.2%. The 1-year overall survival rate was 47.2 % (estimated median survival: 9 months). Significant prognostic factors for survival included: i) ≤4 lung metastases (p=0.035), ii) unilateral lung metastases (p=0.039), iii) primary tumor diameter <100 mm (p<0.001), and iv) ECOG performance status <1 (p=0.015). CONCLUSION: RT is safe and effective for stage IVB UCC patients with lung metastases.

Outcome of postoperative radiation therapy for cholangiocarcinoma and analysis of dose-volume histogram of remnant liver.

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.

Acute and late toxicities in localized prostate cancer patients treated with low-dose 125I brachytherapy (110 Gy) in combination with external beam radiation therapy versus brachytherapy alone (160 Gy).

PURPOSE: The aim of this analysis was to compare acute and late toxicities between low-dose-rate brachytherapy (LDR-BT) (110 Gy) in combination with 45 Gy in 25 fractions external beam radiation therapy (EBRT) and LDR-BT (160 Gy) alone for localized prostate cancer. MATERIAL AND METHODS: One hundred five consecutive patients with localized prostate cancer treated from May 2014 to May 2017 were included in this retrospective analysis. Sixty patients received combination therapy and 45 patients received BT monotherapy. The LDR-BT procedure was performed using 125I seeds. RESULTS: The median follow-up time was 28 months in both groups. Three-year effect rates were overall survival: 100% in both groups. The biochemical failure rate was 2.3% in the combination group and 0% in the monotherapy group (p = 0.373). No patients died during the study period. In both groups, almost all the patients experienced acute urethritis. There was a significant difference between the combination therapy group (8.3%) and BT monotherapy group (11.1%) in late genitourinary (GU) toxicities ≥ grade 2 (p = 0.035). Only 2 patients (3.3%) in the combination therapy group developed late ≥ grade 2 rectal hemorrhage. There were no significant differences between two groups in hematuria ≥ grade 2 (p = 0.068) or rectal hemorrhage ≥ grade 2 (p = 0.206). CONCLUSIONS: To our knowledge, this is the first report to compare the GU and gastrointestinal toxicities between the combination therapy and BT monotherapy (160 Gy) for localized prostate cancer. Unexpectedly, there were more late GU toxicities (except for hematuria) in the BT monotherapy group.

Archaeal MutS5 tightly binds to Holliday junction similarly to eukaryotic MutSγ.

Archaeal DNA recombination mechanism and the related proteins are similar to those in eukaryotes. However, no functional homolog of eukaryotic MutSγ, which recognizes Holliday junction to promote homologous recombination, has been identified in archaea. Hence, the whole molecular mechanism of archaeal homologous recombination has not yet been revealed. In this study, to identify the archaeal functional homolog of MutSγ, we focused on a functionally uncharacterized MutS homolog, MutS5, from a hyperthermophilic archaeon Pyrococcus horikoshii (phMutS5). Archaeal MutS5 has a Walker ATPase motif-containing amino acid sequence that shows similarity to the ATPase domain of MutSγ. It is known that the ATPase domain of MutS homologs is also a dimerization domain. Chemical cross-linking revealed that purified phMutS5 has an ability to dimerize in solution. phMutS5 bound to Holliday junction with a higher affinity than to other branched and linear DNAs, which resembles the DNA-binding specificities of MutSγ and bacterial MutS2, a Holliday junction-resolving MutS homolog. However, phMutS5 has no nuclease activity against branched DNA unlike MutS2. The ATPase activity of phMutS5 was significantly stimulated by the presence of Holliday junction similarly to MutSγ. Furthermore, site-directed mutagenesis revealed that the ATPase activity is dependent on the Walker ATPase motif of the protein. These results suggest that archaeal MutS5 should stabilize the Holliday junction and play a role in homologous recombination, which is analogous to the function of eukaryotic MutSγ.

The Prognosis of Severe Acute Pancreatitis Varies According to the Segment Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced Computed Tomography: A Multicenter Cohort Study.

OBJECTIVE: The aim of this study was to investigate the outcomes of severe acute pancreatitis (SAP) according to the segment presenting with low enhanced pancreatic parenchyma (LEPP) on early contrast-enhanced computed tomography. METHODS: This was a post hoc analysis of a multicenter, retrospective study conducted at 44 institutions in Japan. Patients diagnosed as having SAP according to the Japanese Severity Score between January 2009 and December 2013 were included. We compared the effect of LEPP in each segment on mortality. RESULTS: A total of 1097 patients were assessed. The numbers of patients with LEPP in the pancreatic head (Ph), body (Pb), or tail (Pt) were 272, 273, and 204 (with some overlaps), respectively. In multivariate analysis, LEPP in Ph and Pt was significantly related to mortality (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11-3.40 [P < 0.05], for LEPP in Ph; OR, 2.44; 95% CI, 1.27-4.67 [P < 0.05], for LEPP in Pt), but LEPP in Pb was unrelated to mortality (OR, 0.70; 95% CI, 0.35-1.37; P = 0.30). CONCLUSIONS: Presence of LEPP in Ph and Pt on early contrast-enhanced computed tomography was independently associated with increased mortality in SAP. These patients require close observation to ensure timely and adequate intervention.

An Assessment of Climate Change Impacts on Los Angeles (California USA) Hospitals, Wildfires Highest Priority.

Introduction Although many studies have delineated the variety and magnitude of impacts that climate change is likely to have on health, very little is known about how well hospitals are poised to respond to these impacts. Hypothesis/Problem The hypothesis is that most modern hospitals in urban areas in the United States need to augment their current disaster planning to include climate-related impacts. METHODS: Using Los Angeles County (California USA) as a case study, historical data for emergency department (ED) visits and projections for extreme-heat events were used to determine how much climate change is likely to increase ED visits by mid-century for each hospital. In addition, historical data about the location of wildfires in Los Angeles County and projections for increased frequency of both wildfires and flooding related to sea-level rise were used to identify which area hospitals will have an increased risk of climate-related wildfires or flooding at mid-century. RESULTS: Only a small fraction of the total number of predicted ED visits at mid-century would likely to be due to climate change. By contrast, a significant portion of hospitals in Los Angeles County are in close proximity to very high fire hazard severity zones (VHFHSZs) and would be at greater risk to wildfire impacts as a result of climate change by mid-century. One hospital in Los Angeles County was anticipated to be at greater risk due to flooding by mid-century as a result of climate-related sea-level rise. CONCLUSION: This analysis suggests that several Los Angeles County hospitals should focus their climate-change-related planning on building resiliency to wildfires. Adelaine SA , Sato M , Jin Y , Godwin H . An assessment of climate change impacts on Los Angeles (California USA) hospitals, wildfires highest priority. Prehosp Disaster Med. 2017;32(5):556-562.

Effect of strontium ions on calcification of preosteoblasts cultured on porous calcium- and phosphate-containing titanium oxide layers formed by micro-arc oxidation.

Strontium (Sr) ions were added to calcium- and phosphate-containing porous titanium oxide layers formed by micro-arc oxidation (MAO) of titanium (Ti) substrates to improve their osseointegration. An MC3T3-E1 preosteoblast was used to evaluate the effect of the incorporated Sr species on cell calcification. Similar surface microporous morphologies of the oxide layers were observed for all specimens produced by MAO, while the contents of the incorporated Sr ions increased with increasing Sr concentrations in MAO electrolytes. The calcium- and phosphate-containing porous layers promoted the cell alkaline phosphatase (ALP) activity, while cell calcification was promoted by the Sr addition. In particular, the ALP activity significantly increased after 10 days of culture, and larger areas of calcified deposits were observed for the specimens treated with MAO electrolytes containing 0.15 mol L(-1) of Sr species. The effect of Sr addition on the calcification of the MAO-treated Ti oxide layers was established in this study.

Histochemical Detection of Arylsulfatase Activity in Sea Urchin Embryos: (arylsulfatase/sea urchin embryo/histochemistry/electron microscopy).

Localization of arylsulfatase activity in the sea urchin embryo was determined histochemically by light and electron microscopy. Histochemical observations by light microscopy revealed that the arylsulfatase activity appears after the gastrula stage and that it is restricted to the cells of the aboral ectoderm. The enzyme activity is mainly located in the apical cellular cytoplasm and is associated with lysosome-like structures that are frequently fused with yolk granules. Intense activity is also detected in the region of the endoplasmic reticulum and Golgi apparatus. No enzyme activity is found in the extracellular spaces of embryos.