ICR Group Research Articles

Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis

BackgroundCalorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily...

Complete versus incomplete revascularization in patients with a non-ST-elevation myocardial infarction: Analysis from the e-ULTIMASTER registry

BackgroundIncomplete revascularization (ICR) has been associated with a worse prognosis after a percutaneous coronary intervention (PCI). In NSTEMI patients with multivessel disease (MVD) however, the benefit of a complete revascularization (CR) remains unclear. MethodsPatients presenting with an NSTEMI and MVD were selected from the global e-ULTIMASTER registry and grouped according to completeness of revascularization at index hospitalization discharge. The primary endpoint was the patient oriented composite endpoint (POCE) defined as all death, any myocardial infarction, and any revascularization at 1 year. Target lesion failure (TLF) was defined as the composite of cardiac death, target vessel related myocardial infarction and clinically driven target lesion revascularization. Inverse propensity score weighting (IPSW) was performed to harmonize the patient's baseline characteristics between the groups. ResultsCR was achieved in 1800 patients (47.0 %) and ICR in 2032 patients (53.0 %). The incidence of POCE at 1 year was lower in the CR group compared to the ICR group: 7.0 % vs. 12.9 %, p < 0.0001. Similarly for TLF at 1 year: 3.6 % vs. 5.5 %, p < 0.01. After IPSW, the incidence of POCE was 7.7 % vs. 12.0 %, p < 0.0001, due to a lower all-cause mortality: 2.7 % vs. 4.2 %, p = 0.02 and less revascularizations: 4.9 % vs. 7.9 %, p < 0.001. The incidence of TLF was no longer statistically significant: CR 3.9 % vs. IR 5.0 %, p = 0.10. ConclusionsPatients with a NSTEMI and multi vessel disease undergoing a percutaneous coronary revascularization with a complete revascularization during index hospitalization have better 1-year clinical outcomes. Randomized studies are warranted to confirm these results.

Twelve Weeks of Intermittent Caloric Restriction Diet Mitigates Neuroinflammation in Midlife Individuals with Multiple Sclerosis: A Pilot Study with Implications for Prevention of Alzheimer's Disease.

Multiple sclerosis (MS) is a prototype neuroinflammatory disorder with increasingly recognized role for neurodegeneration. Most first-line treatments cannot prevent the progression of neurodegeneration and the resultant disability. Interventions can improve symptoms of MS and might provide insights into the underlying pathology. To investigate the effect of intermittent caloric restriction on neuroimaging markers of MS. We randomized ten participants with relapsing remitting MS to either a 12-week intermittent calorie restriction (iCR) diet (n = 5) or control (n = 5). Cortical thickness and volumes were measured through FreeSurfer, cortical perfusion was measured by arterial spin labeling and neuroinflammation through diffusion basis spectrum imaging. After 12 weeks of iCR, brain volume increased in the left superior and inferior parietal gyri (p: 0.050 and 0.049, respectively) and the banks of the superior temporal sulcus (p: 0.01). Similarly in the iCR group, cortical thickness improved in the bilateral medial orbitofrontal gyri (p: 0.04 and 0.05 in right and left, respectively), the left superior temporal gyrus (p: 0.03), and the frontal pole (p: 0.008) among others. Cerebral perfusion decreased in the bilateral fusiform gyri (p: 0.047 and 0.02 in right and left, respectively) and increased in the bilateral deep anterior white matter (p: 0.03 and 0.013 in right and left, respectively). Neuroinflammation, demonstrated through hindered and restricted water fractions (HF and RF), decreased in the left optic tract (HF p: 0.02), and the right extreme capsule (RF p: 0.007 and HF p: 0.003). These pilot data suggest therapeutic effects of iCR in improving cortical volume and thickness and mitigating neuroinflammation in midlife adults with MS.

Randomized Clinical Trial of Intermittent Calorie Restriction in People with Multiple Sclerosis: Effects on Immunometabolic and Cognitive Measures

Abstract BACKGROUND: Intermittent calorie restriction (iCR) reduces inflammation in preclinical models and in people with Multiple Sclerosis (pwMS). Mechanisms could be related to changes in levels of adipose tissue-derived adipokines with reduced systemic inflammation and gut microbiota composition. AIMS: Evaluate the effects of iCR on adipokines levels, metabolic and immune/inflammatory biomarkers compared to a control unrestricted diet (Ctr) in pwMS. METHODS: PwMS (relapsing Remitting MS) were randomly assigned to the iCR or Ctr groups for 12 weeks. Blood was collected at baseline, 6 and 12 weeks. Leptin and adiponectin levels, peripheral blood metabolic and immunologic profiling, anthropometric and total body fat measures, and clinical and cognitive measures were evaluated. Differences between iCR and Ctr were examined using a linear, repeated measures mixed model and adjusted for baseline levels, age, sex and DMTs. RESULTS: 42 pwMS were randomized (iCR=22 and Ctr=20). 34 pwMS completed the study (iCR=17 and Ctr=17). PwMS on iCR showed a significant reduction of anthropometric (weight and BMI) and body adiposity measures (waist circumference and fat mass) over the 12 weeks. Leptin levels decreased and were significantly lower in the iCR group at 6 weeks and approaching significance at 12 weeks. Adiponectin increased from baseline in the iCR group at 6 and 12 weeks. The iCR group showed a significant decrease in Th1 cells and an increase in CD45RO+ regulatory T cells after 6 weeks. Cognitive testing using symbol digit modality test showed significantly greater improvement in the iCR group versus Ctr at 12 weeks. CONCLUSIONS: Short term iCR is safe and feasible in pwMS, and it can ameliorate metabolic, immunologic, and cognitive profiles. National Multiple Sclerosis Society # RG-1607-25158

Association between complete revascularization of the coronary artery and clinical outcomes in peripheral artery disease: a sub-analysis of the I-PAD Nagano registry

Peripheral artery disease (PAD) is commonly caused by atherosclerosis and has an unfavorable prognosis. Complete revascularization (CR) of the coronary artery reduces the risk of major adverse cardiovascular event (MACE) in patients with coronary artery disease (CAD). However, the impact of CR in patients with PAD has not been established to date. Therefore, we evaluated the impact of CR of CAD on the five-year clinical outcomes in patients with PAD. This study was based on a prospective, multicenter, observational registry in Japan. We enrolled 366 patients with PAD undergoing endovascular treatment. The primary endpoint was MACE, defined as a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. After excluding ineligible patients, 96 and 68 patients received complete revascularization of the coronary artery (CR group) and incomplete revascularization of the coronary artery (ICR group), respectively. Freedom from MACE in the CR group was significantly higher than in the ICR group at 5 years (66.7% vs 46.0%, p < 0.01). Multivariate analysis revealed that CR emerged as an independent predictor of MACE (Hazard ratio: 0.56, 95% confidential interval: 0.34–0.94, p = 0.03). CR of CAD was significantly associated with improved clinical outcomes in patients with PAD undergoing endovascular treatment.

Long term survival in patients with human papillomavirus-positive oropharyngeal cancer and equivocal response on 12-week PET-CT is not compromised by the omission of neck dissection

Background and AimThe aim of this study was to evaluate the long-term safety of the omission of immediate neck dissections (IND) in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) achieving a less than complete nodal response on 12-week FDG PET-CT. Material and MethodsPatients with HPV-positive, node-positive HNSCC that were treated with radical (chemo) radiotherapy (RT) between January 2013 and September 2019 were identified. PET-CT responses were classified as complete (CR), incomplete (ICR) or equivocal (EQR) nodal responses. Clinical outcomes were obtained. Results347 patients were identified. Median follow-up was 43.9 (IQR, 30.8–61.2) months.62.8% (218/347) achieved a CR, 23.4% (81/347) EQR and 13.8% (48/347) ICR nodal response.70 of 81 (86.4%) patients with an EQR and 25 of 48 (52.1%) with an ICR had no residual disease during follow up (a pathologically negative ND if surgery undertaken or no subsequent neck or distant relapse clinically/radiologically).Median survival of the EQR and CR groups were not reached, and despite the omission of IND in 95% of the EQR group there was no statistically significant differences in overall survival (OS) between the groups, p = 1.0.Median survival of ICR was not reached. However, OS for ICR group was significantly worse than that of CR, and EQR, both p < 0.001. ConclusionThe omission of IND in those achieving an EQR nodal response does not compromise long-term survival. This supports the safety of extended surveillance in patients with HPV-positive disease and an EQR on 12-week FDG PET-CT.

Removal of Indwelling Catheter Following Benign Laparoscopic Hysterectomy: Does Timing Matter?

Study Objective It is standard procedure to place an indwelling catheter during a benign laparoscopic hysterectomy. However, timing of removal after surgery remains controversial due to risk of UTI and recatheterization. This study investigated if the timing of foley removal influenced clinical outcomes and factors influencing timing of removal. Design Retrospective study. Setting Single center hospital. Patients or Participants 281 women that underwent benign laparoscopic hysterectomy in 2018 and did not require bladder suspension and concomitant vaginal surgery. Interventions Foley removal occured either immediately after surgery in the operating room (ICR), or delayed catheter removal (DCR) either in the post-anesthesia care unit (PACU) – (DCR-PACU) or on post-operative day one (DCR-POD1). Measurements and Main Results There were 108 patients in the ICR group, 22 patients in the DCR-PACU group and 151 patients in the DCR-POD1 group. Baseline characteristics such as BMI, age, indications for hysterectomy, uterine weight, and ASA class were similar. DCR-POD1 group patients had longer operative times compared to ICR and DCR-PACU, 158 vs 120 vs 115 minutes, (p-value Conclusion Although ICR was associated with higher urinary retention rate, this did not appear to be statistically significant when the use of scopolamine patch and case complexity was controlled for. ICR should still be considered so as to maximize the benefits of minimally invasive surgery and increase patient satisfaction.

Effect of intermittent versus continuous calorie restriction on body weight and cardiometabolic risk markers in subjects with overweight or obesity and mild-to-moderate hypertriglyceridemia: a randomized trial

BackgroundIntermittent calorie restriction (ICR) is a novel method of dietary restriction for body weight control with the potential to improve obesity-related cardiometabolic markers, but the impact of this diet on subjects with hypertriglyceridemia (HTG) remains unknown.MethodsEighty-eight subjects with overweight or obesity and mild-to-moderate HTG were randomized to the continuous calorie restriction (CCR) group, or ICR group (a very low-calorie diet during 3 days of the week) for 8 weeks (44 patients in each group). Body composition, plasma lipids, glucose, insulin, adiponectin, and liver enzymes were measured at baseline and after 8 weeks. An intention-to-treat analysis was performed.ResultsThe body weight decreased in both groups (4.07 ± 1.83 kg in the CCR group and 4.57 ± 2.21 kg in the ICR group) with no significant difference between the groups. There was no significant difference between the two groups in the reduced amount of fat mass, fat-free mass, and waist circumference. Both groups achieved a significant reduction in plasma triglycerides after 8 weeks (by 15.6 and 6.3% in ICR and CCR groups, respectively) with no difference between treatment groups. HOMA-IR improved significantly in ICR compared to the CCR group (P = 0.03). Plasma glucose, insulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, liver enzyme, and adiponectin were not different between the two groups.ConclusionsThe results of this short-term study suggest that three-days a week of the ICR is comparable to a CCR diet for the reduction of triglycerides level in patients with HTG and in the short-term it appears to be more effective than continuous dieting in improving insulin resistance. However, longer-term studies are needed to confirm these findings.Trial registrationTrial registration number:NCT04143971.

Impact of the residual SYNTAX score on clinical outcomes after percutaneous coronary intervention for patients with chronic renal insufficiency.

ObjectivesThis study demonstrated the prognostic value of the residual SYNTAX score (rSS) for patients with chronic renal insufficiency (CRI).BackgroundThe rSS has been proposed as a useful tool for quantifying and stratifying the degree and complexity of residual stenosis and predicting long‐term clinical outcomes following percutaneous coronary intervention (PCI). However, it has never been validated for patients with CRI.MethodsA total of 2,468 consecutive patients with an estimated glomerular filtration rate <90 ml/min/1.73 m2 who underwent PCI were retrospectively enrolled. Patients with rSS >0 were defined as having incomplete revascularization and were stratified into the reasonable incomplete revascularization (RICR; 0 < rSS ≤ 8) group or the incomplete revascularization (ICR; rSS >8) group. Their outcomes were compared to those of the complete revascularization (CR) group.ResultsDuring follow‐up (median, 3 years; range, 1.5–5 years), the ICR group had the highest incidence of all‐cause death, cardiac death, myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiovascular and cerebrovascular events (MACCE). Despite having higher rates of unplanned revascularization and MACCE, RICR group had comparable all‐cause mortality, cardiac mortality, MI, and stroke with CR group. A multivariable Cox analysis indicated that rSS was an independent predictor of cardiac death, MI, unplanned revascularization, stroke, and MACCE. Furthermore, compared with baseline SYNTAX score, rSS had stronger prognostic accuracy when predicting the risk of unplanned revascularization, stroke, and MACCE at the 3‐year follow‐up.ConclusionsThe rSS is a powerful indicator of clinical outcomes and may help determine reasonable levels of revascularization for patients with CRI following PCI.

Prognostic Value of Residual Syntax Score after Percutaneous Coronary Intervention in Multivessel Coronary Artery Disease

Abstract Background Residual SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) Score (RSS) is an objective measure for the assessment of degree and complexity of residual stenosis after the percutaneous coronary intervention (PCI). Aim The study aimed at evaluating the role of angiographic complete (CR) and incomplete (ICR) revascularization on clinical outcomes in patients undergoing PCI for multivessel coronary artery disease (MVCAD). The study sought to investigate the role of initial and residual severity of coronary atherosclerosis in prognostication of patients with MVCAD who underwent PCI. Material and Methods We retrospectively recruited 135 patients having MVCAD who underwent PCI. Coronary angiogram was used to assess the severity of coronary atherosclerosis. From the angiographic data baseline (BSS) and RSS were calculated. Subjects having a RSS of 0 were defined as having CR, and those having RSS &gt; 0 are defined as ICR group. The study population was subgrouped into two groups as follows: CR, 0 (n = 17, 23%); ICR, &gt;0 to 4 (n = 89, 47.2%). Clinical outcomes were measured, which included major adverse cardiac and cerebrovascular events (MACE) at 1 year. Results Among the study subjects mean age was 57.25 ± 17.55. About 76.3% were males, and 23.7% were females. About 89.4% had diabetes, 88.6% had hypertension as risk factors, and 95.8% were smokers.The mean values of BSS and RSS were 20.2 ± 9.2 and 4.1 ± 7.0, respectively. Based on RSS the individuals were divided into two groups as follows: CR, 0 (n = 17, 23%); ICR, &gt; 0 to 4 (n = 89, 47.2%), &gt; 4 to 8 (n = 16, 21.6%), &gt; 8 (n = 13, 17.55%). After 1 year, three patients lost the follow-up. Among the remaining 132 patients, those with higher BSS had more mortality and morbidity, and the difference is statistically significant (MACE in ≥23 vs. &lt;23, p = 0.000755); 10 patients in the ICR group had MACE compared with 1 patient in CR group(5.8% in CR group vs. 8.6% in ICR group, p-value of 0.38); however, the difference was not statistically significant. However, higher RSS acts as an indirect marker of increasing morbidity and mortality when compared within the tertiles, and the difference was statistically significant (RSS 1–4 group vs. &gt; 4 MACE, p = 0.0009559, RSS &lt; 8 vs. &gt;8 MACE, p = 0.00000172). Conclusions This study proved that both BSS and higher RSS help to foretell the risk of adverse clinical outcomes in individuals with MVCAD who underwent PCI. RSS, which is an indirect marker of residual atherosclerosis, that is, ICR, had a positive correlation MACE after PCI.

Effects of oestrogen and Cimicifuga racemosa on the cardiac noradrenaline pathway of ovariectomized rats.

What is the central question of this study? We investigated the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline pathway and Ca2+ -calmodulin-dependent protein kinase II in ovariectomized rats. What is the main finding and its importance? The right stellate ganglion, but not the left, may be associated with decreased left ventricular noradrenaline content in ovariectomized rats. Oestrogen can reverse all changes caused by ovariectomy. Cimicifuga racemosa did not affect left ventricular noradrenaline, but decreased protein expression of β1 -adrenergic receptor and Ca2+ -calmodulin-dependent protein kinase II. The results might explain potential effects of C. racemosa on the cardiovascular system and provide new insights into cardiovascular protection. The aim of this study was to investigate the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline (NA) pathway and Ca2+ -calmodulin-dependent protein kinase II (CaMK II). Forty adult female Sprague-Dawley rats were randomly divided into the following four groups: sham operated (SHAM); ovariectomized (OVX); ovariectomized with oestrogen treatment (E2); and ovariectomized with C. racemosa treatment (iCR). After 4weeks of treatment, the NA content was determined by high-performance liquid chromatography, and dopamine β-hydroxylase (DBH) and noradrenaline transporter (NET) expression were detected by immunohistochemistry. Western blotting was used to determine NET, β1 -adrenergic receptor (β1 -AR) and CaMKII expression. Compared with the SHAM group, body weights, DBH and NET expression in the right stellate ganglia, and NET, β1 -AR and CaMK II expression in the left ventricles of the OVX group were increased, whereas left ventricular NA content was decreased; DBH and NET expression in the left stellate ganglion was not significantly different. The indexes of the E2 group were similar to those of the SHAM group. Moreover, in the iCR group, DBH, NET, β1 -AR and CaMK II expression was decreased; NET expression and NA content of the left ventricle remained unchanged. Our conclusions are as follows. First, the right stellate ganglion, but not the left, may be associated with decreased left ventricular NA content in OVX rats. Second, oestrogen increases the left ventricular NA content and adjusts the expression of DBH and NET in the right stellate ganglion and restores β1 -AR and CaMK II protein expression to normal levels. Third, C. racemosa does not affect left ventricular NA, but decreases the protein expression of β1 -AR and CaMK II.

Comparison of the response using ICR mice derived from three different sources to ethanol/hydrochloric acid-induced gastric injury.

Animal models for gastric ulcers produced by physical, pharmacological and surgical methods have been widely employed to evaluate therapeutic drugs and investigate the mechanism of action of this disease. ICR mice were selected to produce this model, even though several mice and rats have been widely used in studies of gastric ulcers. To compare the responses of ICR mice obtained from three different sources to gastric ulcer inducers, alterations in gastric injury, histopathological structure, and inflammation were measured in Korl:ICR (Korea NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid (HCl) solution. Firstly, the stomach lesion index gradually increased as the EtOH concentration increased in three ICR groups. Moreover, a significant increase in the level of mucosal injury, edema and the number of inflammatory cells was similarly detected in the EtOH/HCl treated group compared with the vehicle treated group in three ICR groups. Furthermore, the number of infiltrated mast cells and IL-1β expression were very similar in the ICR group derived from three different sources, although some differences in IL-1β expression were detected. Especially, the level of IL-1β mRNA in 50 and 90EtOH/HCl treated group was higher in Korl:ICR and A:ICR than B:ICR. Overall, the results of this study suggest that Korl:ICR, A:ICR and B:ICR derived from different sources have an overall similar response to gastric ulcer induced by EtOH/HCl administration, although there were some differences in the magnitude of their responses.

Characterization the response of Korl:ICR mice to loperamide induced constipation.

Animal models of constipation induced with drugs and diet have been widely employed to investigate therapeutic effects and the action mechanism of drugs against this disease. ICR mice were selected to produce this disease model through oral administration of loperamide (Lop), even though SD rats are commonly utilized in studies of constipation. To compare the responses of ICR mice obtained from three different sources to constipation inducers, alterations in stool number, histopathological structure, mucin secretion and opioid-receptor downstream signaling pathway were measured in Korl:ICR (Korea FDA source), A:ICR (USA source) and B:ICR (Japan source) injected with low and high concentrations of Lop (LoLop and HiLop). The number, weight and moisture content of stools decreased significantly in the Lop treated group of all ICR relative to the Vehicle treated group. Additionally, decreased mucosa layer thickness, muscle thickness, and mucin secretion were observed in the transverse colon of Lop treated ICR mice, while a similar number of goblet cells and crypt of lieberkuhn were detected in the same group. Furthermore, a similar change in the level of Gα expression and PKC phosphorylation was detected in the Lop treated group relative to the vehicle treated group, while some differences in the change pattern were observed in the B:ICR group. Therefore, these results of the present study provide strong additional evidence that Korl:ICR, A:ICR and B:ICR derived from different sources have a similar overall response to constipation induced by Lop injection, although there were a few differences in the magnitude of their responses.

Effects of Estradiol Valerate and Remifemin on Norepinephrine Signaling in the Brain of Ovariectomized Rats

Aims: We investigated the norepinephrine pathway changes from the locus coeruleus (LC) to the preoptic area of the hypothalamus (POAH) in the brain of ovariectomized rats under low estrogen levels and explored the therapeutic effects of estradiol valerate (E₂) and Remifemin (ICR) on these changes. Methods: 40 female Sprague-Dawley rats were randomly divided into the following groups: surgery with vehicle (SHAM), ovariectomy surgery with vehicle (OVX), ovariectomy with E₂ treatment (OVX + E₂), and ovariectomy with Remifemin (OVX + ICR). After 4 weeks of treatment, we observed the changes by immunohistochemistry. Results: (1) The average optical density of DBH-ir fibers and the number of α₁-adrenoreceptor- and estrogen receptor (ER)α-positive neurons in the main nuclei of POAH were all reduced in OVX rats compared with the SHAM group. The above changes were normalized in all nuclei of the POAH in the E₂ group, while they were normalized in some nuclei in the ICR group. Coexpression of ERα and α₁-adrenoreceptor was observed in the POAH. (2) The number of DBH- and ERα-positive neurons in the LC decreased in the OVX group compared with the SHAM group and increased after treatment with E₂ and ICR. Coexpression of ERα and DBH was observed in the LC. Conclusion: Low estrogen (OVX) altered norepinephrine synthesis in the LC, the projection of norepinephrine fibers and α₁-adrenoreceptor expression in the POAH. Both E₂ and ICR normalized the norepinephrine pathway, but E₂ achieved greater effects than ICR. ICR had different effects in different nuclei in the POAH and its therapeutic effect was better in the LC.

Some notes about FT ICR mass spectrometry

We are presenting the notes on different issues concerning directly or indirectly FT ICR. They were chosen eclectically but all are connected to the Moscow FT ICR group activity in the field during more than 30 years. They are covering FT ICR history in Russia and important contributions of the group to the development of the FT ICR technique culminated by discovery of the dynamic harmonization principle on the bases of supercomputer simulations of ion cloud dynamics in different types of FT ICR cells and implementation of the principal in the cell, demonstrated extreme resolving power and mass accuracy. Limitations and potentials of FT ICR mass spectrometry are discussed.

Effect of Isopropanolic Cimicifuga racemosa Extract on Uterine Fibroids in Comparison with Tibolone among Patients of a Recent Randomized, Double Blind, Parallel‐Controlled Study in Chinese Women with Menopausal Symptoms

Objective. Effect of isopropanolic Cimicifuga racemosa extract (iCR) on uterine fibroid size compared with tibolone. Method. The randomized, double-blind, controlled study in China enrolled 244 patients aged 40–60 years with menopausal symptoms (Kupperman Menopause Index ≥ 15). The participants were treated with either iCR of 40 mg crude drug/day (N = 122) or tibolone 2.5 mg/day (N = 122) orally for 3 months in 2004. Now, we investigated the subset of all women (N = 62) with at least one uterine fibroid at onset of treatment for the effect of iCR (N = 34) on fibroid size compared with tibolone (N = 28) by transvaginal ultrasonography. Results. The median myoma volume decreased upon iCR by as much as −30% (P = 0.016) but increased upon tibolone by +4.7%. The percentage of volume change, mean diameter change and geometric mean diameter change of the iCR group compared to tibolone were statistically significant (P = 0.016, 0.021, 0.016 respectively). Conclusion. Our results suggest that iCR (Remifemin) is a valid herbal medicinal product in patients with uterine myomas as it provides adequate relief from menopausal symptoms and inhibits growth of the myomas in contrast to tibolone.

Renal parenchyma developmental plasticity in mice infected with Schistosoma mansoni, whose mothers were malnourished during lactation

Effects of maternal malnutrition during lactation on the kidneys in mice infected with Schistosoma mansoni. Kidneys from programmed infected mice and their respective controls fed a normal diet (23% protein), a protein-restricted group (PR) (8% protein) and a caloric-restricted group (CR) (according to the PR group intake) evaluated by biometry, morphometry and histopathology. Both PR and CR groups showed a reduction in the number of glomeruli when compared with the control group (CR: −29% vs C; PR: −41% vs C; p<0.05) as well as infected mice (ICR: −32% vs IC; IPR: −47% vs IC; p<0.05). Among infected mice, ICR group showed higher kidney weights (+18% vs IC and +12% vs IPR; p<0.01). The ICR and IPR groups showed largest perimeter and area when compared to the corresponding uninfected group (ICR vs CR: +26%; IPR vs PR: +21%, p<0.05) and area (ICR vs CR: +95%; IPR vs PR: +50%, p<0.05). The ICR group showed an increase of within Bowman (CR vs ICR: +56%, p<0.05), whereas Bowman’s space was reduced (PR vs IPR, −61%; p<0.05). Conclude that malnutrition during lactation programmed the metabolic state of the host, resulting in the evolution of the histology of the renal parenchyma.

Retinoic Acid–Induced Alveolar Regeneration

In emphysema, the lung cannot spontaneously regenerate lost alveolar tissue. Treatment with retinoic acid (RA) in rodent models of emphysema induces alveolar regeneration. However, some animal studies have failed to show regeneration when using different species and strains. We have previously shown that dexamethasone (Dex) treatment of newborn TO outbred strain mice permanently disrupts alveolar development. Later RA treatment restores alveolar architecture to normal. To determine whether this model of alveolar regeneration is strain specific, our protocol was repeated with two new outbred mouse strains. ICR and NIHS mice received Dex from Postnatal Days 4 to P15 (P4- P15). From P46 to P57, mice received RA (2 mg/kg) or vehicle. An additional ICR group received 5x RA (10 mg/kg) from P46 to P57. Control groups received vehicle at both treatment points. All mice were killed at P90 and lung morphology analyzed. Dex-treated ICR and NIHS mice showed increased mean alveolar chord length (Lm) and reduced alveolar surface area (SA) and SA/lung volume (SA/LV) compared with controls. RA-treated NIHS mice showed return of Lm, SA, and SA/LV toward control values, indicating alveolar regeneration. ICR RA group mice did not regenerate, but 5x RA mice showed Lm, SA, and SA/LV values consistent with alveolar regeneration. In conclusion, the Dex-treated mouse model of emphysema is robust and repeatable in different strains. RA-induced alveolar regeneration is not a strain-specific phenomenon. RA dose threshold for inducing alveolar regeneration is higher in ICR mice, suggesting a difference in retinoid pharmacokinetics between strains. These results provide a possible explanation for previous failed studies of RA-induced alveolar regeneration.

Isopropanolic black cohosh extract and recurrence-free survival after breast cancer

To investigate the influence of an isopropanolic Cimicifuga racemosa extract (iCR) on recurrence-free survival after breast cancer, including estrogen-dependent tumors. This pharmacoepidemiologic observational retrospective cohort study examined breast cancer patients treated at general, gynecological and internal facilities linked to a medical database in Germany. The main endpoint was disease-free survival following a diagnosis of breast cancer. The impact of treatment with iCR following diagnosis was analyzed by Cox-proportional hazards models, controlling for age and other confounders. Of 18,861 patients, a total of 1,102 had received an iCR therapy. The mean overall observation time was 3.6 years. Results showed that iCR was not associated with an increase in the risk of recurrence but associated with prolonged disease-free survival. After 2 years following initial diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69 0.99). This effect remained consistent throughout all variations of the statistical model, including subgroup analyses. TNM status was unknown but did not bias the iCR treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. An increase in the risk of breast cancer recurrence for women having had iCR treatment, compared to women not treated with iCR is unlikely.

Specific expression pattern of Fos in the accessory olfactory bulb of male mice after exposure to soiled bedding of females.

The heterogeneous structure of the accessory olfactory bulb (AOB) has been demonstrated immunocytochemically. In this study, we analyzed the expression of an immediate-early gene protein, c-Fos, as a marker of neuronal activity in response to chemosensory cues was analyzed. The number of c-Fos-immunoreactive (Fos-ir) cells was measured in the rostral and caudal zones of the AOB in male ICR mice after exposure to the soiled bedding of female mice. The results revealed no significant difference in the number of Fos-ir cells in the caudal zone of the AOB between exposure to the soiled bedding of female ICR mice (ICR group) and exposure to that of female Balb mice (Balb group). In the rostral zone, however, the number of Fos-ir cells in the glomerular layer and granule cell layer was larger in the ICR group than in the Balb group. The difference in the expression of c-Fos in response to different pheromonal stimuli between the rostral and caudal zones in the mouse AOB has been shown for the first time in this study. These results strongly suggest that the heterogeneous structure of the AOB has an important role in the perception and processing of pheromones.