scholarly journals Perfluorocarbon-based oxygen carriers: from physics to physiology

Author(s):  
Johannes Jägers ◽  
Anna Wrobeln ◽  
Katja B. Ferenz

Abstract Developing biocompatible, synthetic oxygen carriers is a consistently challenging task that researchers have been pursuing for decades. Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current investigations. Although largely chemically and biologically inert, pure PFCs are not suitable for injection into the vascular system. Extensive research created stable PFC nano-emulsions that avoid (i) fast clearance from the blood and (ii) long organ retention time, which leads to undesired transient side effects. PFC-based oxygen carriers (PFOCs) show a variety of application fields, which are worthwhile to investigate. To understand the difficulties that challenge researchers in creating formulations for clinical applications, this review provides the physical background of PFCs’ properties and then illuminates the reasons for instabilities of PFC emulsions. By linking the unique properties of PFCs and PFOCs to physiology, it elaborates on the response, processing and dysregulation, which the body experiences through intravascular PFOCs. Thereby the reader will receive a scientific and easily comprehensible overview why PFOCs are precious tools for so many diverse application areas from cancer therapeutics to blood substitutes up to organ preservation and diving disease.

Author(s):  
Rudrashish Haldar ◽  
Devendra Gupta ◽  
Shweta Chitranshi ◽  
Manish Kumar Singh ◽  
Sumit Sachan

Artificial blood is an innovative concept of transfusion medicine where specifically designed compounds perform the task of transport and delivery of oxygen in the body to replace this function of allogenic human blood transfusion. Several molecules have been developed in the past few decades to achieve this objective and continous refinements are being continuously made in the quest of the ideal blood substitute. Currently, available technology manufactures artificial blood from haemoglobin obtained from outdated human/bovine blood (Haemoglobin Based Oxygen Carriers) or utilizing Perfluorocarbons. These synthetic blood substitutes are advantageous in that they do not require compatibility testing, are free from blood borne infections, have prolonged shelf life and do not require refrigeration. Artificial blood is projected to have a significant impact on the development of medical care in the future. It can complement the current blood products for transfusion and create a stable supply of safe and effective products. It is likely to reduce the requirements of blood transfusions drastically especially in settings of trauma and surgery thereby reducing the reliance on banked donated blood.


2008 ◽  
Vol 44 ◽  
pp. 63-84 ◽  
Author(s):  
Chris E. Cooper

Optimum performance in aerobic sports performance requires an efficient delivery to, and consumption of, oxygen by the exercising muscle. It is probable that maximal oxygen uptake in the athlete is multifactorial, being shared between cardiac output, blood oxygen content, muscle blood flow, oxygen diffusion from the blood to the cell and mitochondrial content. Of these, raising the blood oxygen content by raising the haematocrit is the simplest acute method to increase oxygen delivery and improve sport performance. Legal means of raising haematocrit include altitude training and hypoxic tents. Illegal means include blood doping and the administration of EPO (erythropoietin). The ability to make EPO by genetic means has resulted in an increase in its availability and use, although it is probable that recent testing methods may have had some impact. Less widely used illegal methods include the use of artificial blood oxygen carriers (the so-called ‘blood substitutes’). In principle these molecules could enhance aerobic sports performance; however, they would be readily detectable in urine and blood tests. An alternative to increasing the blood oxygen content is to increase the amount of oxygen that haemoglobin can deliver. It is possible to do this by using compounds that right-shift the haemoglobin dissociation curve (e.g. RSR13). There is a compromise between improving oxygen delivery at the muscle and losing oxygen uptake at the lung and it is unclear whether these reagents would enhance the performance of elite athletes. However, given the proven success of blood doping and EPO, attempts to manipulate these pathways are likely to lead to an ongoing battle between the athlete and the drug testers.


2020 ◽  
Vol 14 (2) ◽  
pp. 108-125
Author(s):  
Apoorva Singh ◽  
Nimisha

: Skin cancer, among the various kinds of cancers, is a type that emerges from skin due to the growth of abnormal cells. These cells are capable of spreading and invading the other parts of the body. The occurrence of non-melanoma and melanoma, which are the major types of skin cancers, has increased over the past decades. Exposure to ultraviolet radiations (UV) is the main associative cause of skin cancer. UV exposure can inactivate tumor suppressor genes while activating various oncogenes. The conventional techniques like surgical removal, chemotherapy and radiation therapy lack the potential for targeting cancer cells and harm the normal cells. However, the novel therapeutics show promising improvements in the effectiveness of treatment, survival rates and better quality of life for patients. Different methodologies are involved in the skin cancer therapeutics for delivering the active ingredients to the target sites. Nano carriers are very efficient as they have the ability to improve the stability of drugs and further enhance their penetration into the tumor cells. The recent developments and research in nanotechnology have entitled several targeting and therapeutic agents to be incorporated into nanoparticles for an enhancive treatment of skin cancer. To protect the research works in the field of nanolipoidal systems various patents have been introduced. Some of the patents acknowledge responsive liposomes for specific targeting, nanocarriers for the delivery or co-delivery of chemotherapeutics, nucleic acids as well as photosensitizers. Further recent patents on the novel delivery systems have also been included here.


Water exchange between insects and their environment via the vapour phase includes influx and efflux components. The pressure cycle theory postulates that insects (and some other arthropods) can regulate the relative rates of influx and efflux of water vapour by modulating hydrostatic pressures at a vapour-liquid interface by compressing or expanding a sealed, gas-filled cavity. Some such cavities, like the tracheal system, could be compressed by elevated pressure in all or part of the haemocoele. Others, perhaps including the muscular rectum of flea prepupae, could be compressed by intrinsic muscles. Maddrell Insect Physiol . 8, 199 (1971)) suggested a pressure cycle mechanism of this kind to account for rectal uptake of water vapour in Thermobia but did not find it compatible with quantitative information then available. Newer evidence conforms better with the proposed mechanism. Cyclical pressure changes are of widespread occurrence in insects and have sometimes been shown to depend on water status. Evidence is reviewed for the role of the tracheal system as an avenue for net exchange of water between the insect and its environment. Because water and respiratory gases share common pathways, most published findings fail to distinguish between the conventional view that the tracheal system has evolved as a site for distribution and exchange of respiratory gases and that any water exchange occurring in it is generally incidental and nonadaptive, and the theory proposed here. The pressure cycle theory offers a supplementary explanation not incompatible with evidence so far available. The relative importance of water economy and respiratory exchange in the functioning of compressible cavities such as the tracheal system remains to be explored. Some further implications of the pressure cycle theory are discussed. Consideration is given to the possible involvement of vapour-phase transport in the internal redistribution of water within the body. It is suggested that some insect wings may constitute internal vapour-liquid exchange sites, where water can move from the body fluids to the intratracheal gas. Ambient and body temperature must influence rates of vapour-liquid mass transfer. If elevated body temperature promotes evaporative discharge of the metabolic water burden that has been shown to accumulate during flight in some large insects, their minimum threshold thoracic temperature for sustained flight may relate to the maintenance of water balance. The role of water economy in the early evolution of insect wings is considered. Pressure cycles might help to maintain water balance in surface-breathing insects living in fresh and saline waters, but the turbulence of the surface of the open sea might prevent truly marine forms from using this mechanism.


2012 ◽  
Vol 17 (1) ◽  
pp. 5-26
Author(s):  
Hans Goller

Neuroscientists keep telling us that the brain produces consciousness and consciousness does not survive brain death because it ceases when brain activity ceases. Research findings on near-death-experiences during cardiac arrest contradict this widely held conviction. They raise perplexing questions with regard to our current understanding of the relationship between consciousness and brain functions. Reports on veridical perceptions during out-of-body experiences suggest that consciousness may be experienced independently of a functioning brain and that self-consciousness may continue even after the termination of brain activity. Data on studies of near-death-experiences could be an incentive to develop alternative theories of the body-mind relation as seen in contemporary neuroscience.


Author(s):  
Faiza Naseer ◽  
Tahir Ahmad ◽  
Kousain Kousar ◽  
Salik Kakar ◽  
Rabia Gul

Among the leading causes of cancer mortality, prostatic adenocarcinoma (PaC) is at second to lung carcinoma, but it is the most commonly happening non-cutaneous malignancy in elderly men in the world. Therapeutic options for PaC depend on age, growth & stage of malignancy, the desired outcomes and shortcomings of available treatment, estimated cost and patient compliance. Patients older than 60 years with a sluggish localized tumor may be placed on active surveillance, otherwise go with transurethral resection of the prostate (TURP), prostate artery embolization (PAE) and pelvic lymphadenectomy with/without radiation therapy. For metastatic PC androgen-deprivation therapy is an option with or without surgery. These agents decline the body’s testosterone production or block its activity by gonadotropin- releasing hormone (GnRH) analogues including leuprolide acetate and goserelin acetate implant. The hormone’s activity can be stopped by androgens antagonist such as flutamide, bicalutamide and nilutamide along with chemotherapeutic agents, such as taxanes (e.g., docetaxel, paclitaxel) but after all the disease relapses in 20-30% of patients. So, new immunological or vaccine-based therapeutic moieties have been investigated to meet the objective of providing selectivity to cancerous cells and desired therapeutic outcomes with less/no harmful effects to normal cells. The chimeric version, oncolytic poliovirus and human rhinovirus i.e. PVSRIPO is most promising feature in cancer therapeutics and activate innate immunity by neutrophils infiltration via PAMP & DAMP pathways while Sipuleucel-T expresses major histocompatibility complex (MHC) which can stimulate CD4+ helper T-cells and CD8+ cytotoxic T-cells and ultimately activate the acquired immunity against cancer cells. In this article, we have discussed the role of genetic predisposition and chemotherapeutic approaches including oncolytic poliovirus for the treatment of PaC in order to better understanding of tumor biology and mechanisms involved in chemotherapeutic drugs based resistance.


2018 ◽  
Vol 14 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Giulia Cossu ◽  
Emilio Loi ◽  
Mauro Giovanni Carta ◽  
Alessia Bramanti

Background: The physical activity has been indicated as an experience that can help achieve positive, self-oriented own body awareness. This awareness is an aspect that tends to get worse with age. Objective: Our study aims to verify the internal consistency of a questionnaire on physical awareness in a sample of Italian elders; a secondary objective is to measure if there is a relationship between physical awareness and perceived level of physical activity. Methods: Cross sectional study on a consecutive sample of elderly people was administered the “Physical Body Experiences Questionnaire simplified for active aging (PBE-QAG)”, inspired by the “Physical Body Experiences Questionnaire”, modified, simplified and adapted to be used in the elderly over 65. To elderly people the International Physical Activity Questionnaire. Cronbach’s alpha was also used to assess internal reliability of the total PBE-QAG. The factor structure was evaluated through Confirmatory Factor Analyses (CFAs). Results: The Cronbach’s alpha was 0.8 for the “body-mind relationship” scale, 0.81 for the “accepting your body” scale, 0.83 for the “awareness of physical skills” scale, and 0.65 for the “awareness of physical limits” scale. Cronbach’s alpha for the total PBE-QAG was 0.89. The CFA indicated a model with the 4 factors (CFI = 0.989, TLI = 0.984, RMSEA = 0.076). People who conducted physical activity assiduously or regularly and over 10 minutes showed a better score to the PBE-QAG than those who declared a sporadic activity and for “less than 10 minute”, respectively. Conclusion: Our study revealed that the PBE-QAG shows an excellent total internal consistency. In the Italian sample of elderly people the questionnaire shows the model with the 4 factors described in literature.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mingzhe Liu ◽  
Lingyun Wu ◽  
Sabine Montaut ◽  
Guangdong Yang

Hydrogen sulfide (H2S) was originally considered toxic at elevated levels; however just in the past decade H2S has been proposed to be an important gasotransmitter with various physiological and pathophysiological roles in the body. H2S can be generated endogenously from L-cysteine by multiple enzymes, including cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in combination with cysteine aminotransferase. Prostate cancer is a major health concern and no effective treatment for prostate cancers is available. H2S has been shown to inhibit cell survival of androgen-independent, androgen-dependent, and antiandrogen-resistant prostate cancer cells through different mechanisms. Various H2S-releasing compounds, including sulfide salts, diallyl disulfide, diallyl trisulfide, sulforaphane, and other polysulfides, also have been shown to inhibit prostate cancer growth and metastasis. The expression of H2S-producing enzyme was reduced in both human prostate cancer tissues and prostate cancer cells. Androgen receptor (AR) signaling is indispensable for the development of castration resistant prostate cancer, and H2S was shown to inhibit AR transactivation and contributes to antiandrogen-resistant status. In this review, we summarized the current knowledge of H2S signaling in prostate cancer and described the molecular alterations, which may bring this gasotransmitter into the clinic in the near future for developing novel pharmacological and therapeutic interventions for prostate cancer.


1986 ◽  
Vol 56 (3) ◽  
pp. 545-554 ◽  
Author(s):  
A. J. H. Van Es ◽  
Lisette De Groot ◽  
J. E. Vogt

1. Complete 24 h energy and nitrogen balances were measured for eight subjects both while consuming a basal diet supplemented with 49 g saccharose/d (diet S) and while consuming the same basal diet but supplemented with 50 g lactitol monohydrate/d (diet L).2. The subjects ate the two diets for 8 d. Faeces and urine were collected for the final 4 d. Exchange of respiratory gases (oxygen, carbon dioxide, hydrogen and methane) was measured during the final 72 h while the subjects stayed in an open-circuit respiration chamber, 11 m3, and simulated office work. Before eating diet L, subjects ate 50 g lactitol daily for 10 d.3. On diets L and S, faecal moisture content averaged 0.787 and 0.753 g/g respectively, the difference being significant (P < 0.05). On diet L, energy and nitrogen digestibilities and energy metabolizability averaged 0, 922, 0.836 and 0-881 respectively, and on diet S 0.935, 0.869 and 0.896 respectively; the differences were also significant (P < 0.05). Urinary energy losses and N balances were not significantly different for the two diets.4. In all subjects only traces of methane were produced but hydrogen production differed significantly (P < 0.05) for diets L and S, being 2.3 and 0.4 litres (normal temperature and pressure)/d respectively.5. Intakes of metabolizable energy (ME) were corrected, within subjects, to energy equilibrium and equal metabolic body-weight. The corrected ME intakes did not show differences between diets. However, when on diet L the subjects were probably less active than when on diet S because differences within subjects of ankle actometer counts between diets showed a high correlation with the corresponding differences in corrected ME intakes (r 0.92). Further correction of ME intake toward equal actometer activity showed a significant (P < 0.05) difference between diets: for maintaining energy equilibrium 5.6 (SE 0.8; P < 0.05) % more ME from diet L was needed than from diet S. The reliability of this 5.6% difference depends on whether or not one ankle actometer gives an accurate picture of the subject's physical activity.6. The energy contribution to the body is clearly smaller from lactitol than from saccharose, certainly due to the effect of lactitol on digestion, and probably also due to the effect on the utilization of ME.


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