PMID: 

Breast. 2019 Dec ;48:89-97. Epub 2019 Sep 19. PMID: 31590108

Abstract Title: 

Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I); an ACCRU trial.

Abstract: 

PURPOSE: This pilot trial aimed to assess if cooling hands and feet with crushed ice during receipt of paclitaxel helps prevent peripheral neuropathy.METHODS: This prospective, randomized trial compared cryotherapy to standard care in patients initiating paclitaxel weekly x 12. For those on cryotherapy, hands and feet were cooled starting 15 min prior to and ending 15 min after each paclitaxel dose. EORTC QLQ-CIPN20 was completed at baseline, weekly x12, then monthly x6. Area under the curve (AUC) was calculated for subscale scores, adjusting for baseline, and compared between arms (Wilcoxon rank-sum test). Cross-study comparisonsused data from 2 prior similarly-conducted neuropathy trials.RESULTS: Forty-six patients were accrued. Three withdrew and one was ineligible. Of the remaining 42 (21 cryotherapy, 21 control), 39 (19 cryotherapy, 20 control) were analyzable for AUC. Cryotherapy was well tolerated, but the AUC of the CIPN20 sensory scores over 12 weeks of paclitaxel was not found to differ between the study arms (mean difference 3.45, 95% CI -3.13 to 10.02, p = 0.26). However, the control arm of the current trial experienced less neuropathy than did the placebo arms of two previous similar trials. When our cryotherapy arm was compared to the combined control arms from all three trials, the cryotherapy arm had less neuropathy (Wilcoxon Rank-Sum p = 0.01).CONCLUSION: While there was no difference in CIPN20 scores identified between the 2 study arms in the current phase II trial, further investigation is needed given that the control arm experienced less neuropathy than was expected.

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PMID: 

Prostate Cancer Prostatic Dis. 2019 Oct 14. Epub 2019 Oct 14. PMID: 31611635

Abstract Title: 

A pilot trial of pembrolizumab plus prostatic cryotherapy for men with newly diagnosed oligometastatic hormone-sensitive prostate cancer.

Abstract: 

BACKGROUND: Monotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer.METHODS: This single-institution, pilot trial recruited 12 patients with newly diagnosed oligometastatic prostate cancer between 2015 and 2016. Patients underwent whole-prostate cryoablation combined with short-term androgen deprivation (eight months) and pembrolizumab (6 doses). The primary clinical endpoints were the number of patients with a PSA level of

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PMID: 

Nihon Yakurigaku Zasshi. 2019 ;154(5):245-248. PMID: 31735752

Abstract Title: 

[Effects of cryotherapy on chemotherapy-induced peripheral neuropathy: self-controlled clinical trial].

Abstract: 

Chemotherapy induced peripheral neuropathy (CIPN) is a numbness or tingling of the hands and feet that occur as a side effect of anticancer drugs including taxanes and platinum drugs. The effective treatments or preventive strategy are not established. Once it develops, symptoms persist for a long time and cause impairment in activity of daily living. Topical cooling is a preventive strategy for side effects of chemotherapy such as hair loss, oral microsites, and skin and nail disorder of the hands and feet. We conducted a clinical trial in breast cancer patients who received paclitaxel treatment to assess the effectiveness of cooling for CIPN prevention. In this study, the individual background factor was standardized using an intra-individual comparison design. In 40 subjects, frozen gloves and socks were applied on the dominant hand and foot from 15 minutes before the anti-cancer drug administration to 15 minutes after the end of administration (total 90 minutes) and compared with non-dominant hand and foot. As a result, clinically and statistically significant differences were observed for changes in tactile threshold evaluated by the monofilament test, subjective symptoms, and changes in dexterity evaluated by functional test. The current cooling system has not been well implemented in oncology field due to the lack of facility and human resources. To deliver this therapy broadly, it will be urgent to develop a medical cooling device that can provide safe and effective cryotherapy.

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PMID: 

Mater Sociomed. 2019 Sep ;31(3):212-214. PMID: 31762705

Abstract Title: 

Cryotherapy of Genital Warts.

Abstract: 

Introduction: Genital warts are a frequent form of sexually transmitted disease. Cryotherapy represents the first line of therapy. Healing occurs in 94%, and recurrence in 10% . Side effects are common during the treatment.Aim: The aim of this study is to determine the successfulness of cryotherapy of genital warts, frequency of recurrence, and side effects.Patients and methods: In a retrospective study, data from 50 women with genital warts who were treated in the Gynecological Centre"Dr Mahira Jahić"in Tuzla in a period from 2012-2018 were analyzed. Every woman was treated with cryotherapy. Treatments were repeated every 7 days, maximal number of treatments being 7. In processing of data, X2statistical method was used.Results: 50% (N-25) of genital warts eliminated after 3 treatments with cryotherapy . Genital warts are eliminated in 78% (N-39) of women, while this treatment was unsuccessful in 18% (N-9). Recurrence after 3 months in 4% (N-2). Most common side effect was exudation in 78% (N-39), swelling in 72% (N-36) and pain in 66% (N-33). PAP smears in women with genital warts in 64% (N-34) of cases were inflammatory benign changes, while in 36% (N-18) mild abnormal changes in cells ASCUS and LSIL were found. LSIL lesions of cervix are more common (p

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PMID: 

QJM. 1999 Apr ;92(4):193-8. PMID: 10396606

Abstract Title: 

Improved antioxidative protection in winter swimmers.

Abstract: 

Adaptation to oxidative stress is an improved ability to resist the damaging effects of reactive oxygen species, resulting from pre-exposure to a lower dose. Changes in uric acid and glutathione levels during ice-bathing suggest that the intensive voluntary short-term cold exposure of winter swimming produces oxidative stress. We investigated whether the repeated oxidative stress in winter swimmers results in improved antioxidative adaptation. We obtained venous blood samples from winter swimmers and determined important components of the antioxidative defense system in the erythrocytes or blood plasma: reduced and oxidized glutathione (GSH and GSSG), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat). The control group consisted of healthy people who had never participated in winter swimming. The baseline concentration of GSH and the activities of erythrocytic SOD and Cat, were higher in winter swimmers. We interpret this as an adaptative response to repeated oxidative stress, and postulate it as a new basic molecular mechanism of increased tolerance to environmental stress.

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PMID: 

Biomed Res Int. 2019 ;2019:2065346. Epub 2019 May 15. PMID: 31223612

Abstract Title: 

The Effectiveness of the Whole Body Cryotherapy Strategies: A Comparison of Different Duration and Temperature on the Antioxidative Status in the Experimental Rat Model.

Abstract: 

Background: We examined the effectiveness of the systemic cryotherapy in terms of the temperature and duration of the therapeutic series measured by oxidative stress markers in the rat animal model.Methods: Antioxidants in serum, plasma, liver, and erythrocytes were evaluated in two study groups following 1 min exposure to – 60°C and – 90°C, for 5 and 10 days.Results: Superoxide dismutase activity in the tissues was lower than in the serum. The glutathione peroxidase was significantly higher in – 60°C than in – 90°C, in both 5 and 10 days of exposition. The liver catalase CAT were significantly lower in – 60°C when compared to – 90°C for 5 and 10 sessions of exposure. In all analysed tissues, the sessions of cryotherapy, – 60/5 and – 60/10, were more effective in reduction malondialdehydethan sessions of – 90/5 and – 90/10. The highest total antioxidant capacity was observed in the – 60/5 group.Conclusions: Whole body cryotherapy based on temperature – 60°C may be considered as more beneficial than – 90°C for most of the oxidative stress (OS) markers measured in the selected tissues. The temp. – 60°C is more beneficial than – 90°C when measured by activity of Total SOD, CAT, and GPx. The therapeutic sessions – 60/10 and – 60/5 were the optimal schemes of WBC model in terms of TAC and MDA amount.

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PMID: 

Arctic Med Res. 1992 Jan ;51(1):3-9. PMID: 1562293

Abstract Title: 

Changes in the glutathione system of erythrocytes due to enhanced formation of oxygen free radicals during short-term whole body cold stimulus.

Abstract: 

The red cell glutathione levels of 10 healthy volunteers who are accustomed to winter-swimming were measured before and after this short-term whole body exposition to hypothermic environment. From the increases of the erythrocytic level of oxidized glutathione (GSSG) and of GSSG: total glutathione ratio an extensive formation of oxygen free radicals during and following the exposition to the intensive cold stimulus was concluded. That is in accordance with the finding on the drastic decrease of the concentration of uric acid as an important radical scavenger of the human blood plasma. Furthermore, the initial erythrocytic concentrations of reduced glutathione (GSH) and GSSG of subjects accustomed to winter-swimming were compared with those of healthy control persons who are not accustomed to regular winter-swimming. The markedly increased concentration of GSH and the reduced GSSG:total glutathione ratio in the erythrocytes of winter-swimmers reflect the adaptation to a regular oxidative stress. This antioxidative adaptation is postulated as a new basic mechanism of the hardening by exposition to an intensive short-term cold stimulus often applied within the hydrotherapy.

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PMID: 

Free Radic Biol Med. 1994 Mar ;16(3):299-305. PMID: 8063192

Abstract Title: 

Uric acid and glutathione levels during short-term whole body cold exposure.

Abstract: 

Ten healthy subjects who swim regularly in ice-cold water during the winter (winter swimming), were evaluated before and after this short-term whole body exposure. A drastic decrease in plasma uric acid concentration was observed during and following the exposure to the cold stimulus. We hypothesize that the uric acid decrease can be caused by its consumption after formation of oxygen radicals. In addition, the erythrocytic level of oxidized glutathione and the ratio of oxidized glutathione/total glutathione also increased following cold exposure, which supports this hypothesis. Furthermore, the baseline concentration of reduced glutathione was increased and the concentration of oxidized glutathione was decreased in the erythrocytes of winter swimmers as compared to those of nonwinter swimmers. This can be viewed as an adaptation to repeated oxidative stress, and is postulated as mechanism for body hardening. Hardening is the exposure to a natural, e.g., thermal stimulus, resulting in an increased tolerance to stress, e.g., diseases. Exposure to repeated intensive short-term cold stimuli is often applied in hydrotherapy, which is used in physical medicine for hardening.

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PMID: 

Dialogues Clin Neurosci. 2019 ;21(2):139-147. PMID: 31636488

Abstract Title: 

Psychedelic drugs-a new era in
psychiatry?
.

Abstract: 

This article covers the renaissance of classical psychedelic drugs such as psilocybin and LSD plus 3,4-methylene dioxymethamphetamine (MDMA-ecstasy) in psychiatric research. These drugs were used quite extensively before they became prohibited. This ban had little impact on recreational use, but effectively stopped research and clinical treatments, which up to that point had looked very promising in several areas of psychiatry. In the past decade a number of groups have been working to re-evaluate the utility of these substances in medicine. So far highly promising preliminary data have been produced with psilocybin in anxiety, depression, smoking, alcoholism, and with MDMA for post-traumatic stress disorder (PTSD) and alcoholism. These findings have led to the European Medicines Agency approving psilocybin for a phase 3 study in treatment-resistant depression and the Food and Drug Administration for PTSD with MDMA. Both trials should read out in 2020, and if the results are positive we are likely to see these medicines approved for clinical practice soon afterwards.
.

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PMID: 

Chemistry. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31729089

Abstract Title: 

Simultaneous Production of Psilocybin and a Cocktail ofβ-Carboline Monoamine Oxidase Inhibitors in 'Magic' Mushrooms.

Abstract: 

The psychotropic effects of Psilocybe"magic"mushrooms are caused by the L-tryptophan-derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other L-tryptophan-derivedβ-carbolines as their natural products, which was confirmed by 1D and 2D NMR spectroscopy. Stable-isotope labeling with 13C11-L-tryptophan verified the β-carbolines as biosynthetic products of these fungi. In addition, MALDI-MS imaging showed that β-carbolines accumulate toward the hyphal apices.As potent inhibitors of monoamine oxidases, β-carbolines are neuroactive compounds and interfere with psilocybin degradation. Therefore, our findings represent an unprecedented scenario of natural product pathways that diverge from the same building block and produce dissimilar compounds, yet contribute directly or indirectly to the same pharmacological effects.

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