Dimethyl sulfoxide as an excitatory modulator and its possible role in cancer pain management.

Intractable and untreatable pain from cancer remains a challenge for both patients and clinicians. The pain may be related to the disease itself or the consequences of treatment, such as surgery, chemotherapy or radiation therapy. Cancer pain is intense and has a major impact on patients' quality of life and survival. A significant number of patients receiving analgesic therapy with opioids report persisting pain of a higher intensity than the pain in those who were not on this class of drugs. The pathophysiology of pain in cancer patients is complex and remains poorly understood. Several research groups have studied and demonstrated that cancer and cancer-related symptoms may have an underlying problem of membrane hyper-excitability due to over-presentation of sodium channels and glutamate build-up or over-stimulation of glutamate/N-methyl-D-aspartate (NMDA)/α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) system in cancer cells and the body. Dimethyl sulfoxide (DMSO) is a naturally derived, inexpensive, non-toxic solvent and pharmaceutical agent that has been demonstrated to have numerous health enhancing and therapeutic benefits. In the present article, we provide the scientific evidence and substantiate possible application of DMSO as a well-tolerated excitatory modulator in the management of cancer pain.

Lactobacillus rhamnosus cell lysate in the management of resistant childhood atopic eczema.

The number of children suffering from atopic eczema has increased over the past 30 years especially in children between the ages of 2 and 5 years. These is a significant group of eczematous children that are resistant to standard therapy. Babies and children with eczema suffer pain, irritation and disfigurement from the dermatitis. In this study, we have followed 14 cases of pediatric patients (ages of 8 months to 64 months) with a history of resistant eczema for a period of at least six months. All of these children received 300 mg to 500 mg standardized Lactobacillus rhamnosus cell lysate daily as an immunobiotic supplement. The results of this open label non-randomized clinical observation showed a substantial improvement in quality of life, skin symptoms and day- and nighttime irritation scores in children with the supplementation of Lactobacillus rhamnosus lysate. There were no intolerance or adverse reactions observed in these children. Lactobacillus rhamnosus cell lysate may thus be used as a safe and effective immunobiotic for the treatment and prevention of childhood eczema and possible other types of atopy (allergic diseases).

Treating asthma as a neuroelectrical disorder.

The trend in asthma therapy for the last two decades has been based on the suppression of inflammation and bronchodilation via adrenergic agonism or cholinergic antagonism. These strategies help to control asthmatic symptoms but do not lead to a cure. Substantial populations of patients may still have poorly managed symptoms and suffer a decline in quality of life due to the disease. Reversible airflow obstruction and nonspecific airway reactivity are the key features of asthma. Inflammatory changes do not correlate always with symptoms in asthma patients. It is our opinion that the primary defect in asthma is cell membrane excitation-bronchoconstriction and reactivity-rather than inflammation. Our research, clinical experience and the accumulated evidence from medical literature strongly suggest that controlling other excitatory mechanisms such as voltage-gate sodium channel and glutamate receptors in the central nervous system and lung tissue could lead to more effective and safer strategies for asthma prevention and treatment.

Neurobiological effects of melatonin as related to cancer.

Melatonin is a neurohormone naturally found in humans. Melatonin plays a role in maintaining sleep-wake rhythms; supplementation may help to regulate sleep disturbance that occur with jet lag, rotating shift-work and depression. Preliminary study of melatonin has shown potential for use in the treatment of epilepsy, tinnitus, migraine and neurodegenerative diseases. The latest publication in the Journal of Pineal Research by Edward Mills and colleagues has shown a compelling role of melatonin for the treatment of cancer. Melatonin's consistent relationship with cancer has been shown in many studies assessing links between shift work and cancer rates. High levels of melatonin have been linked to slower cancer progression. How melatonin affects cancer remains largely unclear. Although previous studies suggest different possible mechanisms, many of them are far distant from the primary physiological role of melatonin as a neurohormone. Conflicting studies are found on the role of melatonin in neurodegenerative diseases and cancer. In this article, we try to build and substantiate a neurobiological concept for the anticancer effects of melatonin.

Hypothesis of the cause and development of neoplasms.

Cancer, in general, is considered a disease of genetic mutation. Many questions are, however, unanswered. How exactly do mutations occur in the cells? How do gene mutations interface with the cell microenvironment and macroenvironment to create cancer phenotypes? Is mutation the cause of cancer or the consequence of special adaptive responses to aging; hormonal imbalance; physical, chemical and biologic stresses and damage? What makes cancer spread in the body and invade other organs causing death to the patient? In this paper, we hypothesize that the cellular hyperexcitability via stimulation of mineral channels (e.g. sodium voltage-gated channels) and ligand excitatory receptors (e.g. glutamate and other neuron and non-neuronal excitatory receptors) could be a significant causative and pathogenic factor of cancer. Managing hyperexcitatory states of the cells through lifestyle, nutritional changes, phytochemical and pharmaceutical medications theoretically could be a prospective direction in cancer prevention and therapy.

Neuro-bioenergetic concepts in cancer prevention and treatment.

Cancer remains one of the most difficult and elusive disorders to prevent and treat, despite great efforts in research and treatment over the last 30 years. Researchers have tried to understand the pathogenesis of cancer by discovering the single cellular mechanism or pathway derived from a genetic mutation. There are limited efforts made toward discovering a unified concept of cancer. We propose a neuro-bioenergetic concept of cancer pathogenesis based on the central mechanism of cellular hyperexcitability via inducible overexpression of voltage-gated ion channels, ligand-gated channels and neurotransmitters. Exploration of this concept could lead to a better understanding of the cause of cancer as well as developing more effective and specific strategies toward cancer prevention and treatment.

Bronchial epilepsy or broncho-pulmonary hyper-excitability as a model of asthma pathogenesis.

Over the last 20 years, the prevalence of asthma has nearly doubled in industrialized countries. A similar increase has been predicted for the next two decades. Asthma is major illness in terms of morbidity and suffering, asthma is the leading cause of hospitalizations in children under 15 years of age. According to many top experts, asthma is correctly characterized as a syndrome rather than disease. This lack of definition for asthma makes the search for a cause, prevention and potential cure elusive. Episodic airway obstruction and reversible bronchial hyperresponsiveness to non-specific irritants are the major symptoms of asthma. Airway inflammation is now widely accepted as the key factor underlying the pathogenesis of asthma. However, many patients show no signs of inflammation, yet they still have severe airflow limitation and asthma symptoms. The primary clinical symptoms of asthma are attacks of shortness of breath, wheezing, and coughing resulting from excessive and inappropriate constriction of the airway smooth muscle. Our research suggests a possible epileptic or hyper-excitatory condition of bronchial system in asthma pathogenesis. The paroxysmal, spasmodic character of asthma attacks may be similar to seizures. We propose a unified pathogenetic mechanism of asthma as a syndrome of inducible or genetically predisposed membrane hyper-excitability (bronchial epilepsy).